IJCCM October-December 2003 Vol 7 Issue 4 Indian J Crit Care Med July-September 2005 Vol 9 Issue 3

Review Article

Oximes in organophosphorus poisoning

M. A. Cherian,1 Roshini C,2 J. V. Peter,3 A. M. Cherian4
Abstract

Acute organic insecticide poisoning is a major health problem all over the world, particularly in the develop­
ing countries, where organophosphates (OPs) are the most common suicidal poisons with high morbidity
and mortality and account for a large proportion of patients admitted to intensive care units. Other insecti­
cides less commonly used are organocarbamates, organochlorides, and pyrethroids, which are less toxic
and are associated with less morbidity and mortality. Patients with poisoning present with a wide spectrum
of gastrointestinal, neurological, and cardiac manifestations. A strong clinical suspicion is necessary to
make an early diagnosis and to start appropriate therapy. Treatment is primarily supportive and includes
decontamination, anticholinergics, protection of the airway, and cardiac and respiratory support. The use of
oximes has been controversial and may be associated with higher mortality owing to a higher incidence of
type-II paralysis. They may have other toxic side effects. This paper reviews the literature on OP poisoning.

Key Words: Anticholinergics, Manifestations, Organophosphate, Oximes, Poisoning

Introduction tries.[2] There has been a change in the type of agents

Organophosphate (OP) compounds have been used used for suicide attempts, with OP poisoning being seen
worldwide for pest control for over 100 years. They are more and more frequently as compared with phenobar­
the insecticides of choice in the agricultural world and bitone, diazepam, hypnotics, and antidepressants a cou­
are the most common cause of poisoning among the ple of decades ago. In the Christian Medical College
organic insecticides. They are common agents of sui- (CMC) and Hospital, Vellore, India, OP poisoning ac­
cidal and accidental poisoning, as a result of their ready counted for 12% of all admissions to the medical inten­
availability and easy accessibility. Several hundred peo- sive care unit (ICU) and 29% of all poisoning in the early
ple around the world die each year from OP poisoning, 1990s[3] and now accounts for over 70% of all poisonings.
especially in developing countries.[1] Recently, there has In another center 89.75% of patients admitted with poi­
been a renewed interest in OP compounds as these are soning were owing to OP.[4] OP compounds are com­
agents which might be used as chemical weapons. mon suicidal agents in Pakistan,[5] Sri Lanka,[6] and the
other Asian and South East Asian countries.
The WHO estimates that three million cases of poi­
soning occur worldwide, mostly in the developing coun- The OP compounds are popular insecticides because
of their effectiveness and nonpersistence in the envi-
From: ronment owing to their unstable chemical nature. They
1
Merit Care/UND Program, MeritCare Medical Group, Fargo, ND 58122,USA.
2
Launceston General Hospital, Launceston, Tasmania, Australia.
do not persist in the body or environment as do
3

4
The Queen Elizabeth Hospital, Adelaide, S.A 5011, Australia. organochlorides and have become the insecticide group
Department of Medicine, TMM Hospital, Tiruvalla 689101, India.
of choice replacing DDT, an organochloride compound.[7]
Correspondence:
Dr. A. M. Cherian, TMM Hospital, Tiruvalla 689101, Kerala, India.
E-mail: [email protected] OPs are common household insecticides used exten-

Free full text available from www.ijccm.org

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Indian J Crit Care Med July-September 2005 Vol 9 Issue 3 IJCCM October-December 2003 Vol 7 Issue 4

sively by agricultural communities. Seasonal variations Most OPs are well absorbed from skin, oral mucous
in water availability keep these communities in financial membranes, conjunctival mucous membrane, and
debt, driving farmers to suicide by ingestion of agricul­ gastrointestinal and respiratory routes. Subsequently,
tural pesticides that are sold directly over the counter most OP compounds are hydrolyzed by enzymes, the A
and have inadequate regulations controlling their use esterases or paroxonases, which are not inhibited by
and storage. Early and correct diagnosis and treatment OP compounds. These enzymes are found in the plasma
may be life-saving in OP poisoning. It is important to and in the hepatic endoplasmic reticulum and split the
treat cases in hospitals with respiratory support facili­ anhydride, P–F, P–CN, or ester bonds.[10] The metabolic
ties to reduce the morbidity and mortality. products are then excreted in the urine. OP compounds
that bind to acetylcholinesterase block the conversion
Historical Perspective of acetylcholine to its degradation products, namely,
The first OP compound synthesized in 1854 was acetic acid and choline. This leads to a build-up of ex­
tetraethyl pyrophosphate (TEPP). It came into use in cessive acetylcholine at synapses, which is the primary
Germany during World War II as an agricultural pesti­ cause of most of the toxic effects of OP compounds.
cide substitute for nicotine and for possible use as a
nerve gas in chemical warfare. It is also the most toxic Pathophysiology of OP Poisoning
of the OP insecticides.[8] Parathion, an organic deriva­ Acetylcholine is the neurotransmitter released by the
tive of phosphoric acid, was synthesized shortly after terminal nerve endings of all postganglionic
World War II. Because it has to be converted to paraoxon parasympathetic nerves and in both sympathetic and
by substitution of oxygen for sulfur to be physiologically parasympathetic ganglia. It is also released at the skel­
active, symptoms of parathion intoxication are often de­ etal myoneural junctions and serves as a neurotrans­
layed for 6–24 h. There have been numerous OP com­ mitter in the central nervous system.[11] Acetylcholineste­
pounds synthesized over the years and over a hundred rase is present in two forms: true cholinesterase which
compounds are currently available under different brand is found primarily in the nervous tissue and erythrocytes
names, making identification difficult in a given patient, and pseudocholinesterase which is found in the serum
unless the container is brought in by the patient’s rela­ and liver.[9] OPs bind to the active serine residue of acetyl
tive. Of the OP group, Parathion is the most common cholinesterase irreversibly and convert the enzyme into
cause of human poisoning and fatality.[9]
Table 1: Factors determining the onset, duration, and
Pharmacology intensity of OP poisoning
The OP compounds are classified in many ways; one Nature of compound Remarks
Water-soluble Acute and shorter duration of
based on clinical toxicity is as follows:[9] symptoms, e.g., TEPP
1. Agricultural insecticides (high toxicity), for example, Lipid-soluble Delayed and more sustained
effect, e.g., chlorfenthion
TEPP, parathion, phorate, mevinphos, and disulfoton.
Nature of binding
2. Animal insecticides (intermediate toxicity), for exam­ Reversible Short-lived effects
ple, coumaphos, chlorpyrifos, trichlorfon, and ronnel. Irreversible Persistent effects, e.g., parathion
Mode of action
3. Household use or use in golf courses (low toxicity) , Direct agent Direct acetyl cholinesterase
for example, diazinon, malathion, dichlorvos, and inhibition, e.g., sarin
Indirect agent Needs to be converted to active
acephate. metabolite, e.g., parathion
Route/degree of exposure
Cutaneous Chronic toxicity
OPs may also be classified according to their pharma­ Oral/GIT Acute symptoms
cokinetics as given below. Inhaled May be acute or chronic
depending on poison load
Relative toxicity of the compound
Pharmacokinetics Low
The onset, intensity, and duration of pharmacological Intermediate
High
effects that occur after poisoning are determined largely Rate of metabolic degradation
by the factors listed in Table 1. Malathion

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an inactive protein complex, resulting in the accumula­ Neurological Manifestations in OP

tion of acetylcholine at the receptors, leading to Poisoning
overstimulation and subsequent disruption of nerve im­ Neurological manifestations are the most important
pulse transmission in both the peripheral and central sequelae of OP poisoning as a large number of patients
nervous systems. with acute OP poisoning develop neuromuscular weak­
ness requiring prolonged ventilation. Three types of pa­
Etiology of OP Poisoning ralyses are recognized based on the time of occurrence
OP poisoning results either from suicidal or accidental and differ in their pathophysiology.
poisoning or from occupational exposure such as farm­
ing. A large proportion (68%) of patients presented to Type-I Paralysis or Acute Paralysis
the ICU following an acute suicide attempt.[6,8] Most pa­ Type-I paralysis occurs with the initial cholinergic cri­
tients are young (less than 30 years) with a male pre­ sis. This is postulated to be owing to the persistent de­
ponderance.[8,12] Occupational and accidental poisoning polarization at the neuromuscular junction resulting from
occur less commonly in India.[8] blockade of acetylcholinesterase, and usually develops
within 24–48 h. Features include muscle fasciculations,
Clinical Features of Poisoning cramps, twitching, and weakness. These manifestations
Clinical features of acute poisoning occur within 24 h respond to atropine,[14] although it may not fully block
of ingestion of the OP compound. These can be broadly the nicotinic effects. Muscle weakness may have upper
classified as follows. motor neuron manifestations. Muscle paralysis may also
involve the respiratory muscles, leading to respiratory
Muscuranic Effects failure, requiring ventilation. This may be further com­
Cardiovascular: Bradycardia, hypotension. pounded by severe bronchorrhea. Acute respiratory fail­
Respiratory: Rhinorrhea, bronchorrhea, bronchos­ ure has been observed in 33% of patients who presented
pasm, cough. with OP poisoning.[15]
Gastrointestinal: Increased salivation, nausea and
vomiting, abdominal pain, diarrhea, fecal incontinence. Type-II Paralysis or Intermediate Syndrome
Genitourinary: Urinary incontinence. This was first described by Wadia as Type-II paraly­
Ocular: Blurred vision, increased lacrimation, miosis. sis[16] and subsequently described and termed as inter­
Dermatologic: Excessive sweating. mediate syndrome by Senanayake.[17] Since then, there
have been numerous reports of this syndrome.[14,18–21] It
Nicotinic Effects is a clinical entity that develops after the acute choliner­
Cardiovascular: Tachycardia, hypotension. gic crisis, 24–96 h after the poisoning. In the majority of
Musculoskeletal: Weakness, fasciculations, cramps, patients, respiratory insufficiency draws attention to the
paralysis. onset of the syndrome. Cranial nerve palsies and proxi­
mal muscle weakness are observed. There is relative
Central Receptor Stimulation sparing of the distal muscle groups. The reported inci­
Anxiety, restlessness, ataxia, absent reflexes, convul­ dence of this syndrome varies between 8% and 49%.[20–
22]
sions, insomnia, tremors, dysarthria, coma, hyperreflexia,
Cheyne Stokes breathing, respiratory depression, and
circulatory collapse come under this.[13] One of the earliest manifestations in these patients is
the presence of marked weakness of neck flexon with
The end-result may be multisystem manifestations in­ the inability to lift the head from the pillow. This is a reli­
volving the gastrointestinal tract, respiratory system, able test to assess if a patient is likely to develop respi­
cardiovascular system, nervous system, skeletal mus­ ratory muscle weakness and to pre-emptively manage
cles, as well as metabolic effects such as hypo- or respiratory embarrassment. The common cranial nerves
hyperglycemia. involved are those supplying the extraocular muscles.

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Cranial nerves VII and X are less frequently affected. environmental exposure including optic atrophy, degen­
Electromyographic (EMG) studies have shown a com­ eration of retina, defective vertical smooth pursuit move­
bination of pre- and postsynaptic dysfunction of neu­ ments, myopia owing to spasm, or paresis of accommo­
romuscular transmission. Senanayake showed a fade dation. [31] Rare neurological manifestations include
on tetanic stimulation and absence of post-tetanic facili­ Guillian-Barré syndrome,[32] sphincter involvement,[33] iso­
tation.[17] Nerve conduction and EMG studies in our co­ lated bilateral recurrent laryngeal nerve paralysis,[34] and
hort of patients have shown that the primary type of in­ ototoxicity.[35]
volvement is an axonal neuropathy.[23] In addition to the
neuromuscular transmission defect, anterior cell or toxin­ Cadiovascular Manifestations
induced muscular instability appear to play a role in Type- Cardiac manifestations are often the cause of serious
II paralysis. This syndrome persists for approx 4–18 days complications or fatality. A systematic analysis of pa­
and most patients survive this with ventilatory support tients with poisoning showed a wide variety of cardiac
unless infections complicate the course. More studies manifestations.[36]
from CMC, Vellore, have shown that there is a myopa­
thy as evidenced by significant elevation of muscle en­ Electrocardiographic Manifestations
zymes.[24] These include prolonged Q-T corrected (QTc) interval
(67%); elevated ST segment (24%); inverted T-waves
Type-III Paralysis or OP-Induced Delayed Polyneu­ (17%); prolonged PR interval (9%); rhythm abnormali­
ropathy ties such as sinus tachycardia (35%), sinus bradycardia
OP-induced delayed polyneuropathy (OPIDP) is a sen­ (28%), extra systoles (6%), atrial fibrillation (9%), ven­
sory-motor distal axonopathy that usually occurs after tricular tachycardia (4%); and other manifestations such
the ingestion of large doses of certain OP insecticides[25– as noncardiogenic pulmonary edema (43%), hyperten­
27]
or after chronic exposure. Two distinct clinical entities sion (22%), and hypotension (17%).
have been described, one being pure motor polyneu­
ropathy and the other having a mild sensory component Ludomirsky et al.[37] described three phases of cardiac
with a more prominent motor component. A pure sen­ toxicity.
sory neuropathy has not been observed in either single
or repeated acute OP poisoning.[25] Unlike the interme­ Phase 1: A brief period of increased sympathetic tone.
diate syndrome, it usually occurs 2–3 weeks after the Phase 2: Prolonged period of increased
acute poisoning episode and is characterized by distal parasympathetic activity, including atrioventricular block.
muscle weakness with sparing of neck muscles, cranial Phase 3: QT prolongation followed by torsade de
nerves, and proximal muscles. The EMG features are points, ventricular tachycardia, and development of ven­
those of denervation and recovery is delayed for up to tricular fibrillation.
6–12 months. High-dose methyl prednisolone has been
shown to be beneficial in animal studies.[28] A picture similar to myocardial infarction has also been
reported.[38] In a recent study QTc prolongation at ad­
Other Neurologic Manifestations mission was found to be associated with respiratory fail­
Various neuropsychiatric manifestations have been ure and higher mortality.[39] The mechanism of cardiac
described, especially in chronic poisoning.[29] These have toxicity includes a direct toxic effect on the myocardium,
been termed as chronic OP-induced neuropsychiatric overactivity of cholinergic or nicotinic receptors,
disorder, and includes impaired memory, confusion, irri­ hypoxemia, acidosis, electrolyte abnormalities, and high­
tability, lethargy, and psychosis. These manifestations dose atropine therapy.
are usually temporary. Extrapyramidal manifestations
have also been reported in acute poisoning, developing Respiratory Manifestations
for 4–40 days following poisoning and lasting for approx In the acute phase, muscarinic effects of bronchorrhea,
1–4 weeks, including dystonias, resting tremor, cog­ bronchospasm, and laryngeal spasm can result in air­
wheel rigidity, and choreoathetosis.[30] Neuro-ophthalmo­ way obstruction. The nicotinic effects lead to weakness
logical sequlae have been documented after chronic and paralysis of the respiratory and the oropharyngeal

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muscles. Central depression of respiration owing to in­ Management

volvement of cholinergic systems in the brainstem finally Treatment should be initiated immediately on clinical
leads to respiratory arrest.[15] grounds without waiting for blood investigations.

Acute respiratory failure (less than 24 h) was seen in General Measures

33% of patients with acute poisoning.[17] Most patients Decontamination
with intermediate syndrome develop respiratory failure, Decontamination of the skin is very important and it
which requires mechanical ventilation.[15,17] should be done very thoroughly. The patient should be
stripped and washed with soap and water and then with
Gastrointestinal Manifestations ethyl alcohol. This will prevent further absorption through
GI manifestations are the first to appear, and they re­ the skin. Health-care personnel should wear protective
spond well to atropine therapy. Rarely, acute pancreati­ clothing and glasses.
tis has been reported.[40,41] Patients may also have hypo­
or hyperglycemia.[42] Gastric decontamination should be done by forced
emesis if the patient is fully awake or through a gastric
Grading the Severity of OP Poisoning lavage. All patients should also receive 0.5–1 g/kg acti­
Various grading methods are available and these are vated charcoal every 4 h. Sodium sulfate or sorbitol can
helpful in grading severity and in the management of be used as a cathartic. A recent study has shown that
the syndrome.[43,44] We have found, however, that these the addition of serotonin adipinate, a drug that enhances
do not always correlate with outcomes. Some patients the propulsive function of the gastrointestinal tract, re­
who appear to recover 24 h later develop intermediate sulted in a shortening of the toxicogenic phase and a
syndrome. 3.5-fold reduction of mortality.[46]

Diagnosis Airway and Respiration

The diagnosis of OP poisoning is made primarily based The airway should be secured and adequate oxygena­
on the history and a combination of clinical features, in­ tion should be ensured. Atropine can precipitate ven­
cluding the typical odour of the insecticide. Some pa­ tricular arrhythmia in hypoxic patients. On the other hand,
tients may present with nicotinic effects of tachycardia early use of atropine will reduce respiratory secretions,
and mydriasis rather than the anticipated bradycardia improve muscle weakness, and thereby improve oxy­
and miosis. Some poison centers can identify the com­ genation. Careful observation of the respiratory status
pound from the stomach contents. is required as these patients are prone to respiratory
failure during the acute phase and intermediate syn­
Cholinesterase Estimation drome. The important parameters to be monitored on a
True and pseudocholinesterase levels can be esti­ regular basis are (a) symptoms of ocular muscle involve­
mated. The levels are markedly reduced in OP poison­ ment (e.g.; diplopia), (b) neck muscle weakness, (c) res­
ing. Although true cholinesterase levels correlate with piratory rate, (d) tidal volume or vital capacity, (e) single
severity at presentation, pseudocholinesterase levels do breath count, and (f) arterial blood gas estimation or pulse
not.[45] Serial estimations do not correlate with clinical oximetry. Respiratory infections should be anticipated
improvement, and hence these tests are to be used pri­ and treated appropriately. Theophylline is contraindi­
marily to confirm the diagnosis. Other causes of low­ cated in the management of OP poisoning.[9]
serum cholinesterase include parenchymal liver disease,
congestive cardiac failure with hepatomegaly, metastatic Cardiac Monitoring
carcinoma, malnutrition, dermatomyositis, and acute in­ Wide-ranging cardiac manifestations occur, and care­
fection. A 25% or greater depression in red-blood-cell ful hemodynamic and electrocardiographic monitoring
cholinesterase level is taken as the best indicator of OP should be undertaken. Hypoxemia and electrolyte ab­
poisoning.[9] normalities contribute to cardiac complications. Some

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of these may revert with atropine. Ventricular tachycar­ pharmacokinetics of these compounds and different
dia with a prolonged QTc is best treated with electrical oximes used, but these predominantly consisted of in
pacing.[39] Supraventricular tachycardia can be treated vitro studies. A few in vivo studies, animal studies, and
with an IV bolus of short-acting â-blockers. a few case series also exist. Reactivation has been
shown to be complete when oximes are given within 1 h
Specific Therapy of exposure.[52] Its effects are different in different spe­
Anticholinergic Agents cies,[53] and different with different OP compounds.[54]
Anticholinergics are still the mainstay of treatment and There is also variability in their potency with pH and tem­
should be started as soon as the airway has been se­ perature. The rate and magnitude of aging of the en­
cured. Atropine can be started initially as a 2-mg intra­ zyme is also different with different OP compounds.[55,56]
ventricular (IV) bolus and then at doses of 2–5 mg IV Once aging of the enzyme-OP complex has occurred,
bolus every 5–15 min until atropinization is achieved. reactivation of the enzyme is not possible.
The atropine dose in children is 0.05 mg/kg IV with a
maintenance dose ranging from 0.02 to 0.05 mg/kg.[9] It None of the oximes (pralidoxime, obidoxime, Hl6, and
is important to monitor these patients closely to prevent Hlo7) are considered to be universal reactivators. Some
atropine toxicity and have clear end-points for atropini­ are of broader spectrum and the potencies also differ.
zation. Contrary to earlier beliefs, it is no longer neces­ Obidoxime is the most potent with some OP compounds
sary to achieve total atropinization (i.e., full mydriasis, and Hl6 against others.[55] Pralidoxime is generally less
heart rate more than 150/min, and absent bowel sounds). potent.[54–56] Studies have shown that obidoxime is forty,
In our experience a dose which keeps the heart rate at nine, and three times more potent than Hl6, Hlo7, and
approx 100/min, pupils’ midsize, and bowel sounds just pralidoxime, respectively.[55] Other studies have shown
present, maintains adequately atropinization without the that Hlo7 is superior to the other oximes.[56]
risks of hyperexcitability, restlessness, hyperpyrexia and
cardiac complications that are seen with total atropini­ Administration is an important issue, as only the pow­
zation. Some uncontrolled studies have shown that an der form is stable, and once diluted, the oximes lose
atropine infusion, as opposed to bolus doses at inter­ their potency.[57] An autoinjector that can dissolve the
vals, reduces mortality.[47] Bardin and Van Eden [44] have powder for the purpose of IM injection before admission
demonstrated that glycopyrrolate is equally effective with to the hospital has also been recommended. However,
less central nervous system side effects and better con­ in megadose poisoning, even a high dose of oxime may
trol of secretions. The dose of atropine required is maxi­ not be effective in reactivating the enzyme in the first
mal on day 1 and tends to decrease over the next few few days following poisoning.[57] At least in three studies
days. The mean total dose of atropine in our series has oximes have been effective when the poisoning sever­
been 140–167 mg.[48] Atropine does not reverse the ef­ ity was mild.[52,55,58] Cycloserin has been shown to be re­
fects of intermediate and Type-III paralysis. sistant to oxime therapy.[57] It is also possible that the
response to P2AM may be different for the direct as
Oximes opposed to the indirect anticholinesterase agents.
Oximes are nucleophilic agents that are known to re­
activate the phosphorylated acetylcholinesterase by In some studies formation of methemoglobin and cya­
binding to the organophosphorus molecule.[10] The use nide have been shown after IV administration of oximes
of oximes in acute OP poisoning has been a controver­ to dogs especially with impaired renal function.[56,57,59]
sial subject for over two decades. Initial uncontrolled Obidoxime also leads to hepatotoxicity.[52] The reports
studies suggested that oximes (pralidoxime, P2AM) were are conflicting, though a lot work is being done in this
useful in the routine management of OP poisoning.[49,50] field. Pralidoxime is the oxime available in India, is very
A subsequent report by de Silva et al.,[51] studying two expensive, and the least potent of all oximes.
periods of time (one when P2AM was available in their
country and another when it was unavailable), found that A Medline search revealed only few randomized, con­
P2AM did not make any difference to the outcomes. trolled studies.[3,20,48,60,61] In a small, recent study, respi­
Recently, there have been a number of studies on the ratory complications were more in the group treated with

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IJCCM October-December 2003 Vol 7 Issue 4 Indian J Crit Care Med July-September 2005 Vol 9 Issue 3

obidoxime or P2AM.[62] Mortality was 9% (4/43) in the Table 2: Dose-response relationship

group treated with atropine, 50% (6/12) in the group Placebo Single High dose 12 P value
treated with obidoxime and atropine, and there was no dose 1g IV g infusion
Survival
mortality in the group treated with P2AM (eight patients). Alive 52 (94.6) 31 (68.2) 67 (73.7)
Another study, small but randomized, showed that P2AM Dead 3 (5.4) 5 (13.8) 24 (26.3) 0.001
Intermediate
had no effect in moderate and severe poisoning.[63] syndrome
Yes 19 (13.8) 13 (36.1) 36 (61.5)
No 36 (64.5) 23 (63.9) 23 (38.5) 0.004
We did two major randomized, controlled studies with Infections
similar protocols using 12 g of P2AM infusion over 3 Yes 14 (25.4) 10 (27.8) 25 (43.9)
No 41 (74.6) 26 (72.2) 30 (56.1) 0.03
days. The first was 12 g infusion over 4 days vs 1 g at Ventilation
admission and the second was 12 g infusion over 4 days Yes 22 (40) 61 (67) 61 (67)
No 33 (60) 19 (52.8) 30 (33) 0.005
vs placebo.[3,48,60] A higher mortality was observed in the
P2AM group in both the studies. Ventilatory requirement ing and controversial. From the randomized, controlled
and incidence of intermediate syndrome was higher in trials it appears that they have no effect in moderate
the treatment group. Similar results were found when and severe poisoning and do more harm than good.
the two studies were pooled.[64] Also, a dose-response Pralidoxime is the weaker of the oximes, is very expen­
relationship was shown, especially with a higher sam­ sive, and unstable in aqueous solution. The treatment
ple size, when the two studies were pooled together (Ta­ options are anticholinergic drugs and assisted ventila­
ble 2). Logistic regression analysis showed that the only tion, which is often needed. Mortality rate will continue
independently significant variable was obtained on treat­ to be high as long as the patients are managed in hospi­
ment with P2AM, with an odds ratio of 9.2 (P < 0.006). tals without assisted ventilatory facilities. These patients
Age also had a significant effect on the outcome. These should be transferred to a center where a proper ICU
studies concluded that P2AM has no role in the routine facility is available at the earliest. On a national level, a
management of patients with OP poisoning. minimum pesticide list with less dangerous pesticides
made available, phasing out the WHO Class-I and Class-
Scott[65] reported repeated cardiac asystole following II pesticides would be helpful. The use of safer pesti­
P2AM in OP poisoning. A high dose of oximes can pro­ cides should result in fewer deaths.
duce muscle weakness.[66]
References
In a more recent placebo-controlled study done by us,[67] 1. Eddleston M. Patterns and problems of deliberate self poisoning
we used the highest dose of P2AM, as one of the major in the developing world. QJM 2000;93:715–31.
criticisms was inadequate dose in the previous studies 2. Jeyaratnam J. Acute pesticide poisoning, a major health prob-
(12 g per day for 3 days for severe cases and 4 g per
day for 3 days for moderate cases). It was shown that Table 3: Cholinesterase levels by intervention, Type-I
butyryl cholinesterase (BuCHE) did not correlate with paralysis, Type–II paralysis, complications, and mortal­
the severity of poisoning, Type-I or Type-II paralysis, or ity
other complications (Table 3). It also did not differ in Variables N Mean cholinesterase SD P value
level
cases and controls. The number of days and the total Intervention
dose of atropine showed no difference in the two groups. Placebo 11 713.59 827.13 0.426
Treatment 10 886.25 959.60
BuCHE levels increased gradually over days in both Type-I paralysis
groups and there was no difference whether patients Yes 11 1287.73 923.63
No 10 254.7 359.7 0.001
were treated with P2AM or not. The mortality also was Type-II paralysis
similar in both the groups and treatment made no differ­ Yes 11 967.14 716.48
No 10 607.35 1025.97 0.051
ence—only two patients died, both in the severe group, Complications
and they both died of severe nosocomial infections as­ Yes 10 1047.85 700.54
No 11 568.68 982.63 0.024
sociated with ventilation.
Mortality
Alive 19 784.32 916.61
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