Organophosphorus Poisoning - Still a challenging proposition.

Abstract

A prospective study was conducted on patients admitted with organophosphorus (O.P.) poisoning to our unit from May 99 to May'00. Total number of cases admitted were 62, 37 of them were ventilated. 6 of them died during the course of the treatment. The various aspects of treatment, complications, drug options and uncommon problems were evaluated.

Full text

INDIAN JOURNAL OF ANAESTHESIA, FEB. 200240
ORGANOPHOSPHORUS POISONING - STILL A
CHALLENGING PROPOSITION
Dr. N. Krupesh
1
Dr. T. R. Chandrashekar
2
Dr. A. C. Ashok
3
SUMMARY
A prospective study was conducted on patients admitted with organophosphorus (O.P.) poisoning to our unit from May 99 to May’00.
Total number of cases admitted were 62, 37 of them were ventilated. 6 of them died during the course of the treatment. The various
aspects of treatment, complications, drug options and uncommon problems were evaluated.
Keywords : Organophosphorus poisoning, Pancreatitis, Atropine, Pralidoxime (p2am), Glycopyrrolate.
Diaphragmatic Paralysis, Respiratory Failure, Tachycardia,
Hypertension.
(c) CNS effects
Headache, Tremors, restlessness, ataxia, confusion,
slurred speech, seizures and coma.
Aim
The aim of the present study was to evaluate (a)
cause of death (b) role of Atropine and Glycopyrolate (c)
incidence of other rare complications.
Material And Methods
62 patients were admitted in the Intensive Care
Unit from May ‘99 to May‘00.The demography of
the patients were noted. Treatment protocol followed
was, all the patients were given stomach wash and
skin was thoroughly cleansed at the time of admission
with water. Inj.P
2
AM was given to patients who had
consumed phosphates, at a dose of 15 mg./ kg, 8th
hrly. for first 3 days.In some patients who had
increased weakness on 5th or 6th day, P2AM was
restarted for 3 more days at the same dosage and
frequency
2
. Patients were continuously monitored with
ECG, Spo
2
. ABG and chest skiagram were done as
required. Patients were ventilated when the clinical
condition, Spo
2
reading and ABG values were
suggestive of respiratory fail ure
3
. Inj. Atropine was
given to patients who had a heart rate of less than 60
bpm or had convulsions, at a dose of 0.6 mg. IV
bolus and tittrated according to the response.
Inj.Glycopyrrolate was given to patients who had
excessive bronchorrhea at a dose of 0.2 mg. IM stat
and 6th hrly. if required
4
. Patients who had only
excessive salivation were suctioned as frequently as
required. Serum pseudocholinesterase levels were
estimated on admission and repeated depending upon
1. MBBS,DA.,Junior Registrar- Critical Care
2. MD., Incharge - Critical Care.
3. MS, DA., Consulting Surgeon.
Correspond to :
Dr. T.R. Chandrashekar
#979, 25th Main Road, B.S.K. I Stage, 50 feet Road,
Opp. PES College, Bangalore-560 050.
Tel.Ph: 6513800/801/802
Introduction
Organophosphorus poisoning is the most common
poisoning in India because of its easy availability.O.P
compounds produce their effects by inhibiting the action
of acetylcholinesterase enzyme, which leads to an increase
in acetylcholine, in preganglionic and postganglionic
parasympathetic receptors (muscarinic action), sympathetic
preganglionic synapses including adrenal medulla and
neuromuscular junctions (nicotinic action). Acetylcholine
is also a transmitter in central nervous system. The O.P.
compounds are divided into two groups phosphates and
carbamates, which binds to the active amino acid site on
the acetylcholinesterase enzyme serine, and phosphorylate
or carbamoylate it respectively.
The phosphorylated enzyme is very stable, degrades
only after days to weeks, making acetycholinesterase
essentially inactive. Carbamoylated enzyme degrades within
minutes to hours so that the enzyme site is eventually
regenerated.
The OP poisoning effects can be summarized as
1
,
(a) Muscarinic Effects
Salivation, Bronchorrhea, Bronchospasm,
Bradycardia, Lacrimation, Diarrhea, Urination, G.I.distress,
Emesis, Miosis, Excessive sweating.
(b) Nicotinic Effects
Muscle Fasiculations, Cramping, Weakness,
Indian J. Anaesth. 2002; 46 (1) : 40-43
40

KRUPESH, CHANDRASHEKAR, ASHOK : ORGANOPHOSPHORUS POISONING
41
the clinical condition. Routine base line bio-chemical
investigations were done in all patients.
Table 1 :
Name of No. of No. of Average Non- Death Other
the Patients cases no.of ventilated problems
compound ventilated days on
ventilator
Carbamates 23 08 2.1 15 N i l 4 patients had
superficial burns
in gluteal region
thigh and
groin region.
Phosphates 39 29 6.17 10 06 4 patients had
acute
heamorrhagic
pancreatitis
Total 62 37 — 25 06
Observations
62 patients of OP poisoning were admitted to ICU.
The demography of the study sample was, 45 male
patients, 17 female patients age varied from 12-65 years,the
mean age was 24.8 years.
57 of them consumed the poison through the oral
route. 4 had 25 ml of metacid injected parentrally in their
gluteal region. One patient had poisoning due to inhalation
and absorption through skin. The observations are broadly
divided into two categories, Carbamate group and
Phosphate group.
Carbamate Group
All 23 patients in this group had consumed baygon,
8 of them were ventilated. The average number of days
patients were on ventilator was 2.1 days. The average
dose of Atropine used was 0.33 mg. and average dose
Glycopyrrolate used was 0.04 mg. 4 patients required
Inj. Atropine, 2 patients required Inj.Glycopyrrolate and
1 patient required both. 16 of the patients did not require
neither Inj. Atropine nor Glycopyrrolate. The maximum
dose of Atropine used in a single patient was 3 mg. The
maximum dose of Glycopyrrolate used in a single patient
was 0.4 mg. 4 patients who had consumed Baygon
(Aprocarb/Propoxur) had superficial burns on their gluteal
region, in the natal cleft, inner aspects of thigh on the
day of passing first stools after admission.
Phosphate Group
39 patients belonged to the Phosphate group, 29
were ventilated. The average number of days patients
were on ventilator in this group was 6.17 days. The
average dose of Inj.Atropine required was 0.9 mg. and
average dose of Inj.Glycopyrolate required was 0.35 mg.
5 patients required Inj.Atropine, 10 patients required Inj.
Glycopyrolate, 6 patients required both. 18 patients in
this group did not require neither. Atropine nor.
Glycopyrrolate.
Maximum dose of Inj. Atropine and Inj.
Glycopyrrolate used in a single patient, was 12 mg. and
3.2 mg. respectively,and it was in a patient with parentral
O.P. injection. 3 patients who had received Inj.
Glycopyrolate had collapse of the lungs for which
bronchoscopy was done. Most of the patients had excessive
oral secretions when compared to tracheal secretions. 9.6%
of patients died during the course of the treatment, all of
them belonged to phosphate group and were ventilated.
One patient died due to pulmonary embolism, one patient
died due to infection (Patient was Immuncompromised),
one patient died due to hypotension and one patient died
due to ARDS due to aspiration, 2 patient died due to
pancreatitis. 4 patients had pancreatitis, 2 of them died,
2 of them were managed successfully through conservative
management.
Table II:
Name of No. of No. of No. of No. of No. of Maximum
the patients patients patients patients deaths problems
compound requiring requiring requiring requiring due to doses of
Atropine nor Atropine Glycopyrrolate both muscuranic
Glycopyrrolate alone alone effect ATP GLY
Used in a
single patient
Carba- 16 04 02 01 Nil 03 0.4
mate mg. mg.
Phosph- 18 05 10 06 N i l 12 3.2
ates mg. mg .
Total 34 09 12 07
Discussion
92 % of the patients had consumed O.P. compounds
through oral route. In the study group, 73 % of the
patients were males. Patients who had consumed
carbamates were on ventilatory support for less number
of days, as compared to patients who had consumed
phosphates, which is consistent with the less stable bond
formed due to carbomoylation and early reactivation of
acetylcholinesterase. 4 patients had an unusual complication
of, superficial burns on the day of passing their first
stools after consuming the poison. The site of burns
corresponded to the area of contact with the stools. Patients
did not have burns on their face, oral cavity or on the
area where the poison was spilled. pH analysis of the
stools was acidic. Probably baygon forms some unknown

INDIAN JOURNAL OF ANAESTHESIA, FEB. 200242
acidic compounds on degradation and subsequent exposure
to air, which when comes in contact with skin causes
burns.. It was not consistent with the quantity of poison
consumed or any other predictable factors. We are
preventing this now by placing all the patients who have
consumed (Baygon) on a air filled ring cushion, so that
stools do not come in contact with the skin.
In the phosphate group the duration of ventilation
was more, which was consistent with the more stable
phosphorylated bond and longer deactivation of
acetylcholinesterase enzyme. All 6 patients who died belong
to this group. In this group 4 patients developed acute
haemorrhagic pancreatitis. These patients had distension
of Abdomen, pain in the epigastric region, absent bowel
sounds. Serum amylase and Lipase levels were significantly
increased, more in the patients who died. Ultrasound
examination showed free fluid in all four patients, amylase
estimation of the free fluid which was aspirated showed
high value.The mortality in patients with acute
haemorrhagic pancreatitis was 50%, patients died with
progression to ARDS, hypotension and hypoalbuminemia.
One patient also underwent a diagnostic laproscopy, the
findings were consistent with haemorrhagic pancreatitis.
All the patients were treated with Inj.Somatostatin according
to their body weight.
Intramuscular injection of the O.P. compound leads
to severe nicotinic and muscurinic effects. They also lead
to severe local tissue necrosis at the injection site,
sometimes requiring incision and drainage. All the oily
based O.P. compounds need to be removed, even if there
is no infection, to avoid systemic absorption. The dose
of atropine and glycopyrolate used was higher in this
group.
In the carbamate group 46% of the patients did not
require neither Atropine nor Glycopyrrolate. Only 54% of
the patients required Inj. Atropine or Glycopyrrolate.
The average dose of Inj. Atropine used was 0.33 mg. and
the average dose of Inj. Glycopyrrolate used was 0.04
mg. Even in these patients, the maximum dose of Atropine
used in a single patient was 3 mg.,and the maximum dose
of Inj Glycopyrrolate used in a single patient was 0.4mg.
In phosphate group also 60% of patients did not
require neither Atropine nor.Glycopyrrolate. Only 31% of
patients required Inj. Atropine or Glycopyrrolate. The
average dose of Inj. Atropine used was 0.9 mg. and the
average dose of Inj.Glycopyrrolate used was 0.35 mg.
Even in these patients, the maximum dose of Atropine
used in a single patient was 12 mg. and maximum dosage
of Glycopyrrolate used in a single patient was 3.2 mg.
Both the patients had injected the O.P. compound. In the
carbamate group the percentage of patients requiring
antimuscurinic drugs was more, when compared to
phosphate group. This is in contrary to the strong bond
formed by the phosphates.
55% of the patients in both the groups did not
require antimuscurinic drugs. And the maximum dosage
used was also very less compared to other studies
5
. These
drugs only prevent muscuranic effects, which are seldom
life threatening. High doses of Atropine leads to
tachycardia, which leads to reduction in the diastolic time
which inturn leads to decreased Coronary blood flow.
O.P. compounds also have a direct toxic effect on the
heart, thus the compounded effect leads to cardiac failure
and hypotension, which does not even respond to Inotropic
agents. Atropinisation leads to very restless patients who
have to be sedated, increasing the number of days of
ventilation and ICU stay increases. In this study, patients
who received Inj.Glycopyrolate had very thick tenacious
secretions which was difficult to suction and 3 patients (all
IM injection) had collapse of lung and bronchoscopy had
to be done. The levels of pseudocholinesterase did not
correlate well with the clinical condition. In last 1 year,
of our observation we have, found that, patients who had
bradycardia, hypotension and not responding to Atropine,
did not do well and mortality in such patients was high.
Conclusion
Use of Inj. Atropine and Glycopyrrolate should be
restricted to patients who have bradycardia, convulsion
and excessive broncorrhea. Dosage should be tittrated so
that these effects are reversed. Acute haemorrahagic
pancreatitic is a complication of O.P. poisoning, a high
index of suspicion has to be there to diagnose the condition
early and treat them accordingly. Baygon causes a unusual
complication of superficial burns. The cause of which
has to be evaluated in future studies. The final outcome
depends upon timely ventilatory support, p2am and small
doses of antimuscurinic drugs to avoid life threatening
complications.
References
1. Johnson MK, Vale JA. Clinical Management of Acute
Organophosphate poisoning: An overview in “Clinical and
Experimental Toxicology of Organophosphates and Carbamates.
(Ballantyne B,Marrs TC, eds.) Oxford :Butterworth Heinemann,
1992:528-535.
2. O’ Leary JF, Kunkel AM, Jones AH. Efficacy and Limitations
of Oxime- Atropine treatment of Organophosphorus
anticholinesterase poisoning J Pharm Exp. Ther 1961 : 132 : 50-
57.
3. A Goe,S Joseph, et al. Predicting the need for ventilatory
support JAPI 1998 ; Vol. 46, No 9:786-790.

KRUPESH, CHANDRASHEKAR, ASHOK : ORGANOPHOSPHORUS POISONING
43
4. Choi-PT, Quinonez -LG, et al. The use of glycopyrrolate in
a case of intermediate syndrome following acute
organophosphate poisoning Can -J- Anaesth .1998
Apr,45(4) 337-40.
5. Sunder Ram J, Kumar SS, et al. Continuous use of high dose
Atropine in the treatment of OP compound. Poisoning JAPI
1991;39:190-3
6. Singh-S, Batra-YK, et al. Is atropine alone suffucient in acute
severe Organophosphorus poisoning ? Experience of a North
West Indian Hospital .Int-J- Clin -Pharmacol- other 1995 Nov-
33 (11):628-630.
7. Senanayake N, Kara lliedde L. OP insecticide poisoning. BJA
1989; 63:736-50;475-492
8. Namba T, Notle C, et al. Poisoning due to OP insecticides,
Acute and chronic manifestations. AM J Med 1971;50.
9. Worek- F- Backer - M. et al. Reappraisal of indications and
limitaions of oxime therapy in organophosphate poisoning
.Hum-Exp-Thxicol.1997 Aug.16(8):466-72
10. Thiermann H, Szinicz-L, et al. Modern stategies in therapy of
organophosphate poisoning -Toxicol -left. 1999 Jun 30:107
(1-3):223-9
11. Freeman G, Epstein MA. Therapeutic factors in survival after
lethal cholinesterase inhibitition by phosphorous insecticides,
NEIM 1955;253:266-271.
Awards – Medals – 2001 – ISA
Congratulations Winners !!!
1. Rukmani Pandit Award :
Dr. Sukanya Mitra-Chandigarh
Dr. Madhuri A. Bhade- Ahmedabad.
2. ‘Bhoj Raj’ Award :
Dr. L.D.Mishra – Varanasi.
3. KOP’s Award :
(a) Clinical Pharmacology - Dr. A.K.Saxena, New Delhi.
(b) Obstetric Anaesthesia - Dr. Sachin Sha, Baroda.
(c) Cardiac Anaesthesia
(d) Neuro anaesthesia - Dr. D.Raju, Hyderabad.
(e) Paediatrics - Dr. Jagruti Patel, Ahmedabad.
(f) Pain Management - Dr. Vijish Venugopal, Baroda.
(g) Trauma and Critical Care - Dr. Naveen Malhotra, Chandigarh.
4. Best City Branch : - Mangalore (Karnataka).
5. Best state branch : - Delhi.
6. Practioners Forum : -
7. Late. Dr. T.N.Jha and Dr. K.P.Chansoriya Gold Medal and traveling grant :
Dr. C.Sadasivan, Chennai.
Dr. Manu Shankar, Delhi.
8. Best stall Industry Exhibition : Equipments - Usha Drager India.
Drugs – Neon India Ltd.