Bang Med J Khulna 2017; 50 : 3-7

ORIGINAL ARTICLE

Outcome of treatment of OPC poisoning patients with

atropine or atropine plus pralidoxime
SM Kamal1, S Akhter2, SFU Ahmed3, PK Chowdhury4, AKMM Rashid5, MN lslam6

Abstract
Background: Organophosphorus compound (OPC) poisoning is common in
Bangladesh and management facility is not adequate in most hospitals. Both inj.
Atropine and inj. Pralidoxime is used as antidote for the management of OPC
poisoning, although there is controversy regarding benefit of inj. Pralidoxime.
Objective: This randomised clinical trial was conducted to compare the outcome
of OPC poisoning patients treated by inj. Atropine along with supportive measures
and by inj. Atropine plus inj. Pralidoxime along with supportive measures . This
study also evaluated the clinical profile of OPC poisoning patients.
Methods: A total number of 109 patients, admitted in medicine ward in Khulna
medical college hospital during one year period were included in this randomised
clinical trial. The patients were divided into two groups according to alternate day
of admission in the medicine wards. Forty nine patients of group A was treated by
inj. atropine only along with other supportive measures required and group B of
60 patients was treated by inj. atropine plus inj. pralidoxime along with
supportive measures.
Results: 49 patients of group A was treated with atropine alone and 60 patients
in group B was treated with atropine plus pralidoxime. Death rate was 14.28% in
atropine treated group and 16.66% in atropine plus pralidoxime treated group
(p=0.733). The difference in death rate is not statistically significant. Four (8.18%)
patients from atropine treated group and 4 (6.67%) patients from pralidoxime
intervention group developed respiratory failure and ventilatory support was given
in ICU. These 8 patients recovered. But this difference in development of
respiratory failure is not statistically significant (p=0.766). The difference of death
rate between male and female (12.5% Vs 18.87%) is not also significant (p=0.360).
Conclusion: This study reveals that pralidoxime provides no better outcome in
the management of OPC poisoning patients.
Key words: Organophosphorus compound, Poisoning, Atropine, Pralidoxime.

Introduction acetylcholinesterase (AchE) leading to accumu-

Acute OPC poisoning is widespread in agricultural lation of acetylcholine (Ach) at muscarinic and
developing countries. Overall its frequency has nicotinic receptors.4
increased over the years. The toxicity of the agent The OPCs are of two groups: Phosphates and
and paucity of appropriate medical services has Carbamates, which bind to the active amino acid
resulted in high mortality rates.1 Majority of site serine on the acety1cholinesterase enzyme
death occurs following self poisoning.2 OPC and phosphorylate or carbamylate it respectively.
The phosphorylated enzyme is very stable,
poisoning is more commonly seen in rural areas.
degrades slowly after days to weeks, making
Its incidents is 20% to 30% of total poisoning
acety1cholinesterase essentially inactive.
cases as reported in Japan, Taiwan and Carbamylated enzyme degrades within minutes to
Thailand.3 OPC exerts an acute toxic effect on hours so that the enzyme at the site is eventually
central and peripheral nervous system by blocking regenerated.5

1. S M Kamal FCPS, Professor, Department of Medicine, Khulna Medical College, Khulna, Bangladesh.
2. Shamima Akhter Mphil, Lecturer, Department of Pharmacology, Khulna Medical College. Khulna, Bangladesh.
3. Sk Farid Uddin Ahmed DA, Assistant professor, Dept. of Anaesthesiology, KMC.
4. Poritosh Kumar Chowdhury DTCD, Associate professor, Department of Respiratory Medicine, KMC.
5. AKM Mamunur Rashid MD, Associate Professor, Department of Pediatrics, KMC.
6. Md Nazrul Islam FCPS, Junior Consultant, Department of Medicine, KMC.
Bang Med J Khulna 2017; 50 4
OPC poisoning effects can be summarized as: a) according to the alternate day of admission. All
Muscarinic effects- salivation, bronchorrhoea, the OPC poisoning patients of one admission day
bronchospasm, lacrimation, diarrhoea, urination, was put in group (A) and all the admitted OPC
emesis, miosis, excessive sweating. b) Nicotinic poisoning patients of next day was put in group
effects- muscle fasciculation, cramping, weakness,
(B). The patients of group (A) was treated with
diaphragmatic paralysis, respiratory failure,
atropine only and all the patients of group (B) was
tachycardia, hypertension. c) CNS effects-
confusion, seizure and coma.6 treated with atropine plus pralidoxime. All
patients received other supportive therapy with
The treatment options are anticholinergic drug
stomach wash, i.v. fluid, antibiotics, and O2
intravenous atropine, intravenous pralidoxime to
inhalation as required. Every patient was followed
reactivate acetylcholinesterase, supportive
measures and assisted ventilation. Mortality is up by careful clinical examination. Patients
high in hospitals without facilities for assisted developing respiratory failure was identified by
ventilation.7 Pralidoxime was discovered by clinical examination and by using pulse oximetry.
Wilson and Colleagues in 1950 and successfully Sa02 was <80%. in 8 patients, 4 from each group
used for patients with parathione poisoning. Its developed respiratory failure during treatment.
effectiveness has been much debated with many These patients were treated in ICU of Khulna
Asian clinicians for the treatment of OPC medical college hospital and assisted ventilation
poisoning, although WHO recommended its use.8 support was given. Both groups were further
The results of the earlier oxime trials did not analysed from the start of poisoning to arrival at
demonstrate a favourable outcome. Recent trial
hospital and upto recovery.
suggested benefit of pralidoxime in very early
presentation i.e. within six hours of intoxication of Laboratory studies done were: Complete blood
moderately severe OPC poisoning patients. Oximes count, Blood sugar, serum amylase, urine
can produce respiratory depression, cardiac analysis, serum creatinine, and ECG were done
arrhythmia and neurological weakness.9 There according to the need of patient.
has been extensive debate about the effectiveness
Drug: Inj atropine and Inj pralidoxime was
of oximes for the treatment of organophosphorus
insecticide poisoning. Asian doctors have reported supplied from hospital store and purchased by the
no benefit from pralidoxime.10 Intravenous patient from market when required. Each ampoule
pralidoxime is being used along with intravenous of inj atropine contained 0.6 mg atropine sulphate
atropine for the treatment of OPC poisoning for at and each vial of inj. pralidoxime contained
least one decade in many hospitals of Bangladesh. pralidoxime 1gm. Both drugs were used in iv
We found no study in Bangladesh comparing the route. Inj. pralidoxime was given as intravenous
effectiveness of atropine and pralidoxime, in the infusion over 4 minutes to avoid hypotension.
management of OPC poisoning patients. Both antidotes were administered as per
This experimental study was conducted to see the recommended dosage schedule.
usefulness of pralidoxime in the treatment of OPC Study parameters: All data regarding particulars
poisoning patients. This study also reveals the of patient, clinical features including serious
clinical profile of OPC poisoning patients. manifestations such as fasciculation, respiratory
Materials and methods failure, adverse effects of drugs, complications and
outcome of treatment in each patient were
Selection of patients: This study was a collected in predesigned proforma.
randomised clinical trial. All patients with
organophosphorus compound poisoning admitted Statistical analysis: All data collected in writing
were entered, saved and analyzed in SPSS
in medicine ward of Khulna medical college
programme version 22. Frequency and percentage
hospital, Khulna, Bangladesh from 15 January
were calculated for age distribution, gender
2013 to 14 January 2014, were enrolled for this
distribution, cause of poisoning, treatment
study. During this one year period 109 OPC
outcome as recovery and mortality. p. value was
poisoning patients were admitted. Informed
calculated by chi square test and the p <0.05 was
consent was taken from the guardian of each considered as statisticaly significant.
patient. The detail history was taken and clinical
examination was performed. The medical data of Result
each patient was recorded in writing. In this experimental study a total of 109 OPC
Ethical approval: Ethical clearance from ethical poisoning patients were included. Age of these
review committee of Khulna medical college was patients was from 13 to 90 years. The age
taken for this randomised clinical trial. distribution of the patients are shown in table 1.
The incidence of poisoning was highest 33
Treatment plan: The total number of patients were (30.27%) in 13-18 years age group.
109 and they were divided into two groups
Bang Med J Khulna 2017; 50 5

Table I management with assisted ventilatory support in

Khulna medical college hospital ICU. All these 8
Age distribution of OPC poisoning patients
patients recovered. Out of 109 patients 17 died
Age of the patient No. of % of and the mortality rate is 15.60%. Death rate is
in years patients patients higher among female (18.87% vs 12.50%), but it
13-18 33 30.27 fails to attain statistical significance (p=0.360).

19-24 30 27.53 Table III

25-30 26 23.88 The causes and baseline data of patients
31-36 6 5.5
Causes of Male Female Total
37-42 3 2.75
poisoning Married Unmarried Married Unmarried
43-48 4 3.66
Familial dis-
49-54 6 5.5
harmony 15(13.76) 8(7.33) 18(16.5) 7(6.42) 48(44.03)
55-60 0 0 Non-
61-66 0 0 specific 3(2.25) 6(5.50) 11(10.09) 5(4.58) 25(22.93)
67-72 0 0 Social
problems 2(1.83) 8(7.33) 5(4.58) 1(0.91) 16(14.67)
73-78 0 0
Love
79-84 0 0 rejection - 8(7.33) - 3(2.75) 11(10.09)
85-90 1 0.91 Failure in
Total 109 100 examination - 2(1.83) - 3(2.75) 5(4.58)
Psychiatric
disease 2(1.83) 1(0.91) - - 3(2.75)
Sex distribution revealed that 56 (51.38%) Accidential
patients were male and 53 (48.62%) patients were ingestion - 1(0.91) - - 1(0.91)
female. In our study there is slightly higher Total 22(20.18) 34(31.19) 34(31.19)19(17.44) 109(100)
mortality rate among female (18.87% Vs 12.50%)
but this fails to attain statistical significance
(p=0.360) (Table II). It reveals that survival rate is higher (42-85.72%)
Table II and death rate is lower (7-14.28%) in group A
patients treated with atropine alone. Survival rate
Sex distribution and outcome of treatment is lower (50-83.34%) and death is higher (10-
Sex Total No. & Recovery Death No. p value 16.66%) in group B patients treated with atropine
% patients No. & % &% plus pralidoxime. Atropine with pralidoxime
intervention group shows high mortality rate in
Male 56(51.38) 49(87.50) 7(12.50) comparison with atropine alone (16.66% Vs
Female 53(48.62) 43(81.13) 10(18.87) 0.360 14.28%) but this difference is not statistically
Total 109 92 17(15.60) significant (p=0.733) and we can conclude that
pralidoxime intervention reveals no better
outcome.
The causes of OPC poisoning were identified as far
Although higher rate of ventilation is observed in
as possible. The highest incidence of 48 (44.03%)
atropine treated group (8.16% Vs 6.67%) this
patients was due to various familial problems. In a
significant number of cases (25-22.93%) the cause difference is not statisticaly significant (p=0.766).
was non-specific, unknown and 16 (14.67%) were The outcome of the management is shown in the
due to psychosocial problems. Baseline data of the table IV below.
patients was also shown in Table III Table IV
This study included 109 patients of OPC Outcome of management of OPC poisoning patients
poisoning. The patients were divided into two
Treatment No. of Reco- Death p Respi- p
groups according to the alternate day of options patients very (%) No. (%) valuefailure value
admission. Group A of 49 patients was treated & ventil
with the antidote Inj atropine iv and another
group B of 60 patients was treated with inj Atropine 49 42(85.72) 7(14.28) 0.733 4(8.16)
atropine iv plus inj pralidoxime iv. All these 0.766
Atropine+ 60 50(83.34) 10(16.66) 4(6.67)
patients received other supportive measures as
Pralidxime
needed. Total 8 patients, 4 from each group
developed respiratory failure and was given ICU Total 109 92 17(15.60) 8
Bang Med J Khulna 2017; 50 6
Discussion atropine treated group (8.16% Vs 6.67%), this
OPC is a pesticide and used in agricultural difference is not statistically significant (p=0.766)
country like Bangladesh for saving crops from the So it is observed that 8(100%) patients survived
attack of insect. So this pesticide is kept in rural when ventilatory support in ICU was provided.
and also in urban houses. Some people ingest this This experimental study suggests that better
highly poisonous compound to do self harm, even outcome regarding death of OPC poisoning can be
suicide. Death occasionally occurs due to achieved if ICU management with ventilatory
respiratory failure. Intravenous atropine and support can be made available in the hospitals of
intravenous pralidoxime is used as anti dote along Bangladesh.
with gastric lavage and other supportive
We can also analyse the profile of OPC poisoning
measures. Assisted ventilation for respiratory
patients shown in this study. The causes of OPC
paralysis is given in few centers where facility is
poisoning are multifactorial. Most common cause
available. But there is controversy regarding the
is familial disharmony (44.03%), other causes are
effectiveness of pralidoxime. Experimental study
social problems, failure in examination,
reveals that pralidoxime is effective only in mild
psychiatric disorder, love rejection and accidental
cases of OPC poisoning and pralidoxime is
ingestion of OPC. In a significant number 25
generally less potent.11,12 Reactivation of
(22.93%) of cases the cause of poisoning could not
acetylcholinesterase (AchE) is shown to be
be identified.
complete when oximes are given within one hour
of poisoning.13 One study in India described the This study revealed that OPC poisoning is a bit
development of myopathy after the use of higher in male 51.38% (56) than in female about
pralidoxime.14 In the Bangladeshi scenario the 48.62% (53). Mortality rate is 15.60%. Death rate
admission of OPC poisoning patient is late. So it is is higher among female (18.87% vs 12.50%), but it
rarely possible for us to use pralidoxime within fails to attain statistical significance (p=0.360).
one hour of poisoning. In our study a total of 109 In this study we observed that addition of
patient was included. Among them one group of pralidoxime did not increase the survival rate in
49 patient was treated with atropine alone. Out of comparison to the patients group treated with
these patients 42 (85.72%) recovered and 7 atropine alone. So this experimental study
(14.28%) died. Another group of 60 patient was suggests that this costly drug pralidoxime is not
treated with atropine plus pralidoxime Out of necessary in the treatment of OPC poisoning
these patients 50 (83.34%) recovered and 10 patients. Further large scale study can be done
(16.66%) died. Atropine plus pralidoxime using pralidoxime in patients with mild toxicity of
intervention group shows high mortality rate in OPC and in patients admitted in hospital within
comparison with atropine alone (16.66% Vs one hour of ingestion of OPC.
14.28%) but we can not conclude clearly that
There is limitation of this study as we did not
combination therapy is inferior to atropine
observed the effectiveness of pralidoxime by
(p=0.733). However we can conclude that
administering it within few hours of ingestion of
pralidoxime intervention gives no better outcome.
OPC.
Clinical trial in India with atropine alone and
atropine plus pralidoxime reveals that difference Conclusion
in the rate of mortally is not significant (p value The benefit of pralidoxime is insignificant in the
>0.05). So the study concluded that pralidoxime in treatment of OPC poisoning patients. This
treatment of moderate to severe OPC poisoning experimental study reveals that addition of
does not add any advantage over atropine.15 Our pralidoxime did not decrease the death rate of
study also reveals similar result. During this OPC poisoning patient. Death rate can be
study pralidoxime was administered in patients markedly decreased if adequate ICU management
with mild, moderate and severe toxicity of OPC with ventilatory support can be given in all the
poisoning irrespective of their duration of medical college hospitals.
poisoning, that means in case of early and also in
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