A DISSERTATION ON
A CLINICAL STUDY OF SERUM AMYALSE IN ORGANOPHOSPHORUS POISONING IN A TERTIARY CARE HOSPITAL
Submitted to THE TAMILNADU DR. M. G. R. MEDICAL UNIVERSITY CHENNAI
In partial fulfilment of the regulations for the award of M.D DEGREE IN GENERAL MEDICINE BRANCH I
Register No. : 201711409
GOVERNMENT MOHAN KUMARAMANGALAM MEDICAL COLLEGE, SALEM
MAY 2020 Government Mohan Kumaramangalam Medical College Hospital
DECLARATION BY THE CANDIDATE
I hereby declare that this dissertation titled “A CLINICAL STUDY OF
SERUM AMYLASE IN ORGANOPHOSPHORUS POISONING IN A
TERTIARY CARE HOSPITAL” is a bonafide and genuine research work carried out by me under the guidance of Dr. S.SURESHKANNA, M.D.,
Professor, Department of General Medicine, Government Mohan
Kumaramangalam Medical College Hospital, Salem, Tamil Nadu, India.
Place : Salem Signature of the Candidate Date : Dr R.VINOTH
Government Mohan Kumaramangalam Medical College Hospital
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This is to certify that this dissertation “A CLINICAL STUDY OF
SERUM AMYLASE IN ORGANOPHOSPHORUS POISONING IN A
TERTIARY CARE HOSPITAL” is a bonafide work done by Dr.R.VINOTH in partial fulfillment of the requirement for the degree of M. D. in General medicine, examination to be held in May 2020
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Date : Dr. S.SURESHKANNA, M.D Professor Department of Medicine, Government Mohan Kumaramangalam Medical College Hospital, Salem, Tamil Nadu.
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SERUM AMYLASE IN ORGANOPHOSPHORUS POISONING IN A
TERTIARY CARE HOSPITAL” is a bonafide work done by Dr. R.VINOTH under the overall guidance and supervision of Dr.S.SURESH KANNA , M.D.,
Professor, Department of General Medicine, Government Mohan
Kumaramangalam Medical College Hospital, in partial fulfillment of the requirement for the degree of M. D. in General Medicine, examination to be held in May 2020.
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TERTIARY CARE HOSPITAL” is a bonafide work done by Dr.R.VINOTH under the guidance and supervision of Dr.S.SURESHKANNA, M.D.,
Professor, Department of General Medicine, Government Mohan
Kumaramangalam Medical College Hospital, in partial fulfillment of the requirement for the degree of M. D. in General Medicine, examination to be held in May 2020
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ACKNOWLEDGEMENT
I am extremely thankful to Prof. Dr.R.BALAJINATHAN., Dean,
Government Mohan Kumaramangalam Medical College Salem, for allowing me to utilize the hospital facilities doing this work.
I would like to express my heartfelt gratitude to my mentor and teacher,
Prof. Dr. S. SURESH KANNA, M.D., Professor, Head of the Department of
General Medicine, Government Mohan Kumaramangalam Medical College
Hospital, Salem, for his encouragements.
I am deeply indebted to Prof. Dr. S.SURESH KANNA, M.D.,
Department of General Medicine, Government Mohan Kumaramangalam
Medical College Hospital, Salem, for his expert guidance throughout the period of the study and postgraduate course.
Warmest and sincere thanks to Professors Dr. D. VIJAYARAJU, M.D,
Dr.J.A.VASANTHAKUMAR, MD, and Dr. M. MANJULA, M.D., and
Dr.V. RAJKUMAR, M.D., for all the help, encouragement and guidance during my post-graduation study period.
I am deeply grateful to all Assistant professors in the department of
General Medicine for their immense help and guidance during my post- graduation course.
I extend my heartfelt thanks to all my colleagues and friends for their help and association, during my study
I specially thank all my patients without whose cooperation; this dissertation would never have seen the light of the day.
TABLE OF CONTENTS
S.No. TOPIC PAGE No.
1. INTRODUCTION 1
2. AIMS AND OBJECTIVES 2
3. REVIEW OF LITERATURE 3 - 62
4. MATERIALS AND METHODS 63 – 64
5. OBSERVATIONS AND RESULTS 65 - 96
6. DISCUSSION 97 – 99
7. CONCLUSION 100
8. SUMMARY 101
ANNEXURES: BIBLIOGRAPHY 102 – 107 CONSENT FORM 108 – 109 STUDY PROFORMA 110 – 112 MASTER CHART 113 - 116
LIST OF TABLES
PAGE S.No. TITLE No.
1. TABLE SHOWING AGE DISTRIBUTION 65
2. TABLE SHOWING SEX DISTRIBUTION 66
3. TABLE SHOWING DISTRIBUTION OF COMPOUND 67 CONSUMPTION
4. TABLE SHOWING VENTILATORY SUPPORT 68
5. TABLE SHOWING CLINICAL OUTCOME 69
6. TABLE SHOWING PUPILLARY CHANGES 70 DISTRIBUTION
7. TABLE SHOWING DISTRIBUTION IN 71 FASCICULATION
8. TABLE SHOWING DISTRIBUTION IN HEART RATE 72
9. TABLE SHOWING DISTRIBUTION IN RESPIRATORY 73 RATE
10. TABLE SHOWING DISTRIBUTION IN MENTAL 74 STATUS
11. TABLE SHOWING DISTRIBUTION IN CONVULSIONS 75
12. TABLE SHOWING SEVERITY BY USING POP SCALE 76
13. TABLE SHOWING RELATION OF PUPILLARY 77 CHANGES WITH S.AMYLASE ON DAY 1 PAGE S.No. TITLE No.
14. TABLE SHOWING RELATION OF PUPILLARY 78 CHANGES WITH S.AMYLASE ON DAY 2
15. TABLE SHOWING RELATION OF FASICULATION 79 WITH S.AMYLASE ON DAY 1
16. TABLE SHOWING RELATION OF FASICULATION 80 WITH S.AMYLASE ON DAY 2
17. TABLE SHOWING MULTIPLE COMPARISONS OF 81 FASICULATION WITH S.AMYLASE ON DAY 1 & DAY 2
18. TABLE SHOWING RELATION OF HEART RATE WITH 82 S.AMYLASE ON DAY 1
19. TABLE SHOWING RELATION HEARTRATE OF WITH 83 S.AMYLASE ON DAY 2
20. TABLE SHOWING RELATION OF RR WITH 84 S.AMYLASE ON DAY 1
21. TABLE SHOWING RELATION OF RR WITH 85 S.AMYLASE ON DAY 2
22. TABLE SHOWING RELATION OF MENTAL STATUS 86 WITH S.AMYLASE ON DAY 1
23. TABLE SHOWING RELATION OF MENTAL STATUS 87 WITH S.AMYLASE ON DAY 2
24. TABLE SHOWING RELATION OF CONVULSIONS 88 WITH S.AMYLASE ON DAY 1
25. TABLE SHOWING RELATION OF CONVULSIONS 89 WITH S.AMYLASE ON DAY 2 PAGE S.No. TITLE No.
26. TABLE SHOWING RELATION OF POP SCALE 90 SEVERITY WITH S.AMYLASE ON DAY 1
27. TABLE SHOWING RELATION OF POP SCALE 91 SEVERITY WITH S.AMYLASE ON DAY 2
28. TABLE CORRELATION OF POP SEVERITY WITH 92 S.AMYLASE ON DAY1 &2
29. TABLE SHOWING RELATION OF VENTILATOR 93 SUPPORT WITH S.AMYLASE ON DAY 1
30. TABLE SHOWING RELATION OF VENTILATOR 94 SUPPORT WITH S.AMYLASE ON DAY 2
31. TABLE SHOWING RELATION OF CLINICAL 95 OUTCOME WITH S.AMYLASE ON DAY 1
32. TABLE SHOWING RELATION OF CLINICAL 96 OUTCOME WITH S.AMYLASE ON DAY 2
33. TABLE SHOWING POP SCALE 111 - 112
LIST OF FIGURES
S.No. TITLE PAGE No.
1. ACETYLCHOLINE SYNTHESIS AND TERMINATION 10
2. ORGANOPHOSPHORUS –STRUCTURE 23
3. WADIA SYNDROME 36
4. ELECTROPHYSIOLOGICAL EFFECTS IN 51 INTERMEDIATE SYNDROME
5. BAR DIAGRAM SHOWING AGE DISTRIBUTION 65
6. PIE CHART SHOWING SEX DISTRIBUTION 66
7. BAR DIAGRAM SHOWING DISTRIBUTION OF 67 COMPOUND CONSUMPTION
8. PIE CHART SHOWING VENTILATORY SUPPORT 68
9. PIE CHART SHOWING CLINICAL OUTCOME 69
10. BAR DIAGRAM SHOWING PUPILLARY CHANGES 70 DISTRIBUTION
11. BAR DIAGRAM SHOWING DISTRIBUTION IN 71 FASICULATION
12. BAR DIAGRAM SHOWING DISTRIBUTION IN 72 HEART RATE
13. BAR DIAGRAM SHOWING DISTRIBUTION IN 73 RESPIRATORY RATE S.No. TITLE PAGE No.
14. BAR DIAGRAM SHOWING DISTRIBUTION IN 74 MENTAL STATUS
15. PIE CHART SHOWING DISTRIBUTION IN 75 CONVULSIONS
16. BAR DIAGRAM SHOWING SEVERITY BY USING 76 POP SCALE
17. BAR DIAGRAM SHOWING RELATION OF 77 PUPILLARY CHANGES WITH S.AMYLASE ON DAY 1
18. BAR DIAGRAM SHOWING RELATION OF 78 PUPILLARY CHANGES WITH S.AMYLASE ON DAY 2
19. BAR DIAGRAM SHOWING RELATION OF 79 FASICULATION WITH S.AMYLASE ON DAY 1
20. BAR DIAGRAM SHOWING RELATION OF 80 FASICULATION WITH S.AMYLASE ON DAY 2
21. BAR DIAGRAM SHOWING RELATION OF HEART 82 RATE WITH S.AMYLASE ON DAY 1
22. BAR DIAGRAM SHOWING RELATION HEARTRATE 83 OF WITH S.AMYLASE ON DAY 2
23. BAR DIAGRAM SHOWING RELATION OF RR WITH 84 S.AMYLASE ON DAY 1
24. BAR DIAGRAM SHOWING RELATION OF RR WITH 85 S.AMYLASE ON DAY 2 S.No. TITLE PAGE No.
25. BAR DIAGRAM SHOWING RELATION OF MENTAL 86 STATUS WITH S.AMYLASE ON DAY 1
26. BAR DIAGRAM SHOWING RELATION OF MENTAL 87 STATUS WITH S.AMYLASE ON DAY 2
27. BAR DIAGRAM SHOWING RELATION OF 88 CONVULSIONS WITH S.AMYLASE ON DAY 1
28. BAR DIAGRAM SHOWING RELATION OF 89 CONVULSIONS WITH S.AMYLASE ON DAY 2
29. BAR DIAGRAM SHOWING RELATION OF POP 90 SCALE SEVERITY WITH S.AMYLASE ON DAY 1
30. BAR DIAGRAM SHOWING RELATION OF POP 91 SCALE SEVERITY WITH S.AMYLASE ON DAY 2
31. PEARSON CORRELATION OF POP SEVERITY WITH 92 S.AMYLASE ON DAY1 &2
32. BAR DIAGRAM SHOWING RELATION OF 93 VENTILATOR SUPPORT WITH S.AMYLASE ON DAY 1
33. BAR DIAGRAM SHOWING RELATION OF 94 VENTILATOR SUPPORT WITH S.AMYLASE ON DAY 2
34. BAR DIAGRAM SHOWING RELATION OF CLINICAL 95 OUTCOME WITH S.AMYLASE ON DAY 1
35. BAR DIAGRAM SHOWING RELATION OF CLINICAL 96 OUTCOME WITH S.AMYLASE ON DAY 2
ABBREVIATIONS
S.NO ABBREVIATIONS EXPANSIONS
1 OPC Organophosphorus compound
2 POP Peradynia Organophosphorus Poisoning Scale
3 IU/L International units per Litre
4 CNS Central nervous system
5 ANS Autonomic nervous system
6 ATP Adenosine Tri phosphate
7 RBC Red blood cell
8 PTMA Phenyl trimethyl Ammonium
9 DMPP Dimethyl phenyl piperazinium
10 DAG Diacyl glycerol
11 NO Nitric oxide
12 CPK Creatine phosphokinase
13 GIT Gastrointestinal Tract
14 LD Lethal Dose
15 WHO World Health Organization
16 DTR Deep Tendon Reflex
17 CSF Cerebrospinal fluid
18 HR Heart rate
19 PAM 2-Pyridine aldoxime methyl chloride
20 CPAP Continuous Positive Airway Pressure
ABSTRACT:
BACKGROUND:
Organophosphorus poisoning is one of the most common poisoning world wide.It produce clinical alterations in the serum amylase. previously plasma cholinesterase are used to assess the severity of poisoning .At present serum amylase is one best indicator to assess the severity of poisoning. The study aim was to estimate serum amylase in organophosphorus poisoning cases and correlation of serum amylase with outcome of patient.
MATERIALS AND METHODS:
It is cross sectional study sample size of 100 patient those who are admitted in our hospital with history of organophosphorus poisoning with clinical features and evidence of poisoning. POP scale and serum amylase were analysed for first 48 hours after poison consumption and their prognostic values were used to assess severity in predicting respiratory failure patients.
RESULTS:
In our study poison consumption is predominant in middle age group between 31-40 years of age(36%).male shows predominant (69%).compound most commonly consumed is monocrotophos (22%).In our study amylase value were significantly increased at the time of admission and shows reduction gradually by treatment. Patients those need ventilator support have increased amylase levels on day 1(403.88 IU/L) compared to patients does not need support (155.47 IU/L) it shows P value is significant <0.0001..And outcome of patients those who are expired showed significantly increased amylase values in day 1 (490.12 IU/L) compared to alive patients (182.70 IU/L) it was also statistically significant.
CONCLUSION:
Serum amylase is considered as marker for organophosphorus poisoning patients. Hence earlier elevation of serum amylase we can predict those who are all risk of developing complications like respiratory failure and require ventilator support.
INTRODUCTION:
Organo Phosphorus compounds is used for insecticidal, herbicidal purposes and also chemical war fares in the form of nerve gas agents. Due to easy availability of the compounds there is increased chance of poisoning is more common in developing countries like India. Nowadays rate of admissions and incidence rate is increased in Opc poisoning cases.
Organophosphorus mainly cause over activation of acetylcholine actions in the form of both muscarinic and nicotinic manifestations as well as CNS manifestation also. organophosphorus compounds which cause increased cholinergic activation from the pancreatic glands leads to increased serum amylase levels. several studies reported elevated serum amylase levels in organophosphorus poisoning patients were closely related to clinical outcome of the patients.
Earlier plasma cholinesterase is used to assess the severity in organophosphorus poisoning patients. Now serum amylase is one of the better indicator to assess the severity.
Earlier identification of those who severily ill and prevent from various complications like respiratory failure, useful in mostly developing countries like
India due to lack of health personnel, infrastructures ,etc.
So the study undertaken to estimate serum amylase in Opc poisoning patients and correlate serum amylase with clinical outcome of the patients using
POP scale.
1
AIMS AND OBJECTIVES:
1 .To estimate serum amylase in organophosphorus poisoning patients
2. To correlate serum amylase with the outcome of the patients
2 REVIEW OF LITERATURE:
Organophosphate poisoning is one of the most poison consumption by world wide.
Around the world three million poisoning cases happened per year out of this two hundred thousand death occur. It is one of the most common suicidal attempt took place in developing countries like India. In INDIA south Indian persons are more commonly affected by organophosphate poisoning compared to north Indian people .persons can exposed to poison by various route like drinking ,inhalational ,skin exposure. organophosphates are usually used for pesticidal purposes .Apart from that it can be used for medical conditions for treating patients like alzhemier disease, myasthenia gravis ,miotics, postoperative decurarization and neurotoxic snake bite cases. And also it is used as nerve gas agents in some of the developed countries .In early 1800 lassiagne first identified these compounds by phosphoric acid reaction with alcohol. Gerhad
Schrader 1 was a germen chemist discovered various special effective insecticides. Bladan is the first fully synthetic contact insecticide Hexaethyl tetraphosphate as a constituent and parathion (E605).In 1936 2 while he was experimenting with a class of compounds called organophosphates, he accidentally discovered Tabun a heavy toxic organophosphate compound. During the second world war, under the Nazi regime teams lead by Schrader ,Ambrose,
Rudiger, Vander linde identified another toxic agent sarin in the year
1938.Richard Kuhn identified one more toxic nerve agent named soman in the year 1944.fourth agent VX is discovered after the world war.
3 G agents tabun ,sarin soman are absorbed into our body via skin route and inhalational route. VX agents are contact poison unless aerosolised contaminate the ground for weeks or months. Both toxicity wise and treatment wise nerve gas agents are like pesticides poisoning only. organophosphate poisoning cause heavy mortality due to various reasons like highly toxicity, delay in hospital arrival by transporting patients, lack of adequate health care workers, lack of infrastructure and lack of training abilities and lack of antidote. carbamates are one more group of toxic compounds are acting like organophosphates but some what different in the mode of action.
Even though suicidal attempt by ingestion of toxic poisoning compound is one of the most common mode of exposure sometimes accidental poisoning can occur in pediatric age group due to keep the poison compound easily to reach in children nearby they get accidentally swallowed the toxic substances.one more accidental route of exposure while working in fields farmers are frequently get exposed by using insecticide to destroy insects in their field, due to lack of knowledge regarding personal protection against this toxic compounds
.Apart from occupationally exposed to this toxic compound by farmers. other common persons like house wife, labourers, students are want to quit their life by using insecticide poison compound due to failures in life in the form of poverty, no job, quarrel with husbands ,failed in examinations and some other social problems prevalent in our community.
4 AUTONOMIC NERVOUS SYSTEM:3
FUNCTION: Autonomic nervous system mainly act as a control of visceral organ functions. Its s somewhat different from somatic nervous system by various features. They are :
1. Apart from the skeletal muscles all other visceral organs are supplied
by Autonomic nervous system.
2. Nerve fibres compared to somatic nervous system preganglionic are
Myelinated and postganglionic fibres are non myelinated.
3. Nerve plexus formation in the peripheral region is intact
4. The distal most synapse is found outside the central nervous system is
within the ganglia.
5. The neurotransmitter which is Efferently acting have Acetyl choline,
Noradrenaline.
6. Eventhough after the nerve section organ which is supplied it does not
show any atrophy of organs instead of it activity maintained.
But it is one point similar with somatic nervous system it has centre, afferent and efferent connections are present.
AUTONOMIC AFFERENTS:
Afferent fibres from the internal organs mostly non myelinated in nature.
LOCATION: cell bodies is usually situated in the dorsal root ganglion of spinal nerves and sensory ganglion of the cranial nerve
5 FUNCTION: it mediates internal organ pain perception. most of the internal organ reflexes, respiratory system reflexes, cardiovascular too.
CENTRAL AUTONOMIC CONNECTIONS: 3
It has no specific autonomic areas in the central nervous system. The most important one which controls the autonomic functions is HYPOTHALAMUS. Of these postero lateral portion of the nucleus mediate sympathetic system ; antero medial portion of the nucleus mediate parasympathetic system. some other autonomic centres are located in the brain stem part which mediate pupillary
,vagal and respiratory reflexes in related to cranial nerve .thoracic spinal cord of these lateral column portion sympathetic outflow system arises.
EFFERENTS: 3 The effector portion of Autonomic nervous system carries information from central nervous system to effector organs like exocrine glands, smooth muscle and cardiac muscle etc. The two major sub divisions are parasympathetic and sympathetic nervous system.in general speaking these two parts are antagonistic in function. but one exception is refractory period of the atrial fibres is decreased by both sympathetic and parasympathetic fibres. Spleen, sweat glands and hair follicles, some blood vessels have sympathetic supply only. ciliary muscle, gastric and pancreatic glands have parasympathetic supply only.one more system related to ANS is Enteric nervous system which innervates the gastrointestinal tract and control the function of that system like integrate bowel movements, secretion and absorption.
SYMPATHETIC SYSTEM: 3
6 It mostly origin from the thoracic portion (T1-T12) and lumbar (L1-L5) region of the spinal cord. compared to parasympathetic nervous system it have broad range of distribution of fibres. almost ganglia of the sympathetic system lies on along the side of the spinal cord in the form of two para vertebral chains. some may located in front of the abdominal aorta. Ganglia are almost away from the internal organs due to this arrangement post ganglionic fibres are longer
.compared to preganglionic, postganglionic fibres ratio is somewhat higher from1:20 to 1:100.The major neuro transmitter is Noradrenaline and minor one is acetyl choline. Nor adrenaline is somewhat stable neurotransmitter have wide range of actions.one of the important function is managing emergency situations and stress .
PARASYMPATHETIC SYSTEM: 3
It originate from the cranial nerve III,VII,IX, X. and sacral portion of the spinal cord (S2-S4).but it has limited range of distribution like head and neck
,trunk portion.
parasympathetic ganglia are situated is some what close to visceral organs, so they have postganglionic fibres is somewhat short in nature. ratio of preganglionic and post ganglionic is 1;1.
Acetylcholine is one of the major neurotransmitter.it gets rapidly destroyed by locally.it main functions is conservation of energy, helps in the assimilation of food.
NEUROTRANSMITTER:
7 Acetyl choline is one of the major neurotransmitter involved in somatic nervous system and sympathetic system involved regulating sweat gland secretion and parasympathetic system of between post ganglionic area and their target cells or organ.
HISTORY:
Acetylcholine 4 was first discovered by henry hallet dale in the year of
1915 by studying its action on cardiac muscle .later one of the fine scientist name
Otto Loewi identified as a Acetylcholine function as a neurotransmitter. He only name the neurotransmitter as a Vagusttoff because it released from the vagus nerve. Later both scientist got noble prize for one of the greatest invention in medicine .acetylcholine is the first neurotransmitter detected .
SYNTHESIS;
Acetylcholine 4 is synthesized by nerve terminals by the enzyme named choline acetyl transferase.it is formed by acetyl coA which is produced by citric acid cycle in the mitochondria, and choline. both are combined in the presence of the above mentioned enzyme .choline usually cross the cell membrane in order to react with acetylCoA. choline was taken up the neurons through Na+: choline co transporter mechanism. first ATP reacts with acetate and co enzyme A forms acetyl coA .
After that choline combined with acetyl coA formed acetylcholine. choline uptake was the rate limiting step involved in the acetylcholine synthesis
8 .this step is inhibited by drug named Hemicholinium which leads to deficiency of acetylcholine.
STORAGE; 4
Acetylcholine is actively get stored in the synaptic vesicle, but some may present in the cytoplasm of nerve terminals. transport of acetylcholine into vesicle mediated by one more transporter named vesicle associated transporter
(VAT).one more drug called vesamicol inhibit this active transport mechanism.
RELEASE OF NEUROTRANSMITTER: 4
Release from the storage site to nerve terminal need calcium entry it took place via calcium channels. After that SNARE proteins interaction involvement leads to vesicles get docked and calcium entry followed by it fused with nerve terminals get acetylcholine release. Two important toxins prevent the release of the neurotransmitter it was Boutlinum toxin and Black widow spider toxin.
TERMINATION OF ACETYLCHOLINE: 4
It was terminated by the enzyme named Acetyl cholinesterase broken down acetylcholine into choline and acetate. End products of the acetylcholine was not excreted it was recycled again in our body.
9 FIGURE OF ACETYLCHOLINE SYNTHESIS;
CHOLINESTERASES:
Two enzyme involved to hydrolyse acetylcholine named Acetyl cholinesterase and Acyl choline acyl hydrolase.
ACETYLCHOLINESTERASE:
It is also know as true cholinesterase or cholinesterase 1.It is present in erythrocytes 3 lungs ,spleen, nerve endings, grey matter of brain and almost all
10 cholinergic sites. Hydrolysis of acetylcholine took place in very fast within micro seconds happened.
WHY DEGRADATION REQUIRED?
Degradation is required for depolarization of nerve so that it can get repolarized to get participate in the upcoming conducting system.
SECOND CHOLINESTERASE:
It is also called by various names pseudo cholinesterase ,semi cholinesterase butrylcholinesterase.it is present in white matter of brain, plasma
,liver, intestine .but its biological role is not known. hydrolysis of acetylcholine is very slow.it was more sensitive to organophosphate inhibition.
BIOCHEMISTRY:5
The both cholinesterase get different in specificity towards some substrate. The serum cholinesterase acts on benzoylcholine but not on acetyl methacholine. It is reversed in the case of RBC cholinesterase it hydrolyse acetyl methacholine but not in benzoylcholine. The genes which control cholinesterase synthesis exist in various allelic forms.6 The following are various allelic forms are
EU- Normal phenotype;
Ea-weakly active towards for most of the substrates in CHE.
Ef-increased resistance for fluoride inhibition.
Es-absence of enzyme, they have little or no catalytic activity.
11 CLINICAL SIGNIFICANCE: 1)
Indicator of pesticide poisoning ;2)As a liver function test ; 3)those who are atypical forms are more prone for prolonged response to some muscle relaxant.
CONDITIONS ALTER THE LEVEL OF ENZYME:6
SERUM CHOLINESTERASE (LOW LEVEL):
1. Acute infections 2. Chronic debilitating disease 3. Cocaine,morphine,codeine 4. Pregnancy 5. Dermatomyositis 6. Genetic deficiency 7. Liver parenchymal disease 8. Oral contraceptives 9. Organic mercury 10. Succinylchloride.
HIGH LEVEL:
1. Nephrotic syndrome.
RBC CHOLINESTERASE: (LOW LEVEL);
1. Antimalarial drugs
2. oral contraceptives.
PRINCIPLE OF SERUM CHOLINESTERASE ESTIMATION:
The principle behind was measurement of production of thiocholine followed by reacts with DTNB(dithiobisnitrobenzoate) produced yellow colour.it can be measured with the help of spectrophotometer at 412nm.
12 CHOLINORECEPTORS:
It can be divided into two types of receptor 1.muscarinic 2.Nicotinic .
MUSCARNIC RECEPTORS:3
These receptors are G protein coupled receptors
LOCATION:
Present in mainly autonomic effector cells like Heart, vascular endothelium, exocrine glands ,smooth muscle, presynaptic nerve terminals.
AGONIST: It was stimulated by muscarine
ANTAGONIST: It was antagonised by Atropine.
NICOTINIC RECEPTORS: 3
These receptors act via ligand gated cation channel
LOCATION:
Present in skeletal muscle end plates and Autonomic ganglia, Adrenal medulla.
AGONIST:
Nicotine, PTMA, DMPP
ANTAGONIST:
These receptors are antagonised by Tubocurarine , Hexamethonium etc.
MUSCARINIC RECEPTOR SUB TYPES:3
It can be classified into five subtypes. of these three are major in nature based on molecular cloning techniques. They are:
1.M1; 2 M2;
13 3.M3 4.M4 5.M5. All are present in both peripheral part of the organ and central nervous system which including pre junctional nerve endings .sometimes based on they function (M1;M3;M5) belongs to one category and (M2;M4) belongs to another category. Most organs of our body usually possessed more than sub type of muscarinic receptor, but for a particular given tissue only one subtype will dominant.
M1 RECEPTOR:3
LOCATION: it is present in certain areas of the central nervous system like corpus striatum, hippocampus, cortex.
MECHANISM OF ACTION: it belongs to G protein coupled receptor of these it is Gq in nature. After Gq protein get attached to membrane bound phospholipase c leads to release of two important chemicals named (DAG)
Diacylglycerol and (IP3) Inosital triphosphate. DAG leads to cause alteration protein kinase C ,cause secretion.. Inosital triphosphate cause release of calcium ions from where they get stored and acts AGONIST : MCN-343 A
;Oxotremorine;
ANTAGONIST: pirenzepine; Telenzepine. Both agonist and antagonist are selective in nature.
ACTION: 1.GASTRIC GLANDS- due to histamine release gastric secretion will produced and relaxation of oesophageal sphincter (LES ) due to vagus nerve stimulation.
14 2.CNS: it plays an important role in higher mental functions like memory, learning process as well as motor functions also.
3.AUTONOMIC GANGLIA: Due to depolarization it cause late excitatory postsynaptic potential.
M2 RECEPTOR: LOCATION :it is present mainly in cardiac group of muscles
,but some receptors also present in smooth muscle, also have Auto receptor function.
MECHANISM OF ACTION: 3 This belongs to Gi group of G protein coupled receptor.it cause potassium channel opening which leads to decrease in second messenger cyclic adenosine monophosphate (c AMP ) cause inhibitory action in most of the target tissues.
AGONIST:
Methacholine.
ANTAGONIST:
Methoctramine;Tripitramine.
ACTION:
SA NODE ; Due to potassium channel opening leads to hyperpolarization of the membrane which leads to decrease in the rate of impulse generation
AV NODE : It cause decrease in the conduction velocity
ATRIUM AND VENTRICLES : It cause shortening of the APD leads to force of contraction is reduced in both atrial musculature and ventricular.
15 NERVE ENDINGS : Due to auto receptor function it cause decrease in
Acetylcholine release.
CNS : it produces involuntary movements like Tremor; and analgesic effect also.
SMOOTH MUSCLE : in visceral smooth muscle it acts on produce contraction.
M3 RECEPTOR:3
LOCATION: it is present in visceral group of smooth muscles, iris , ciliary muscle, exocrine glands, vascular endothelium.
MECHANISM OF ACTION : like M1 receptor it have G protein coupled receptor stimulant activity (Gq). it produces DAG and inositol triphosphate which mediated secretion of these target tissue.
AGONIST:
Bethanechol
ANTAGONIST: Darifenacin, Hexahydrosiladifenidol.
ACTIONS:
IRIS:
It acts on sphincter pupillae to produce constriction of pupil.
CILIARY MUSCLE: It produce contraction of ciliary muscle .
EXOCRINE GLANDS: It mediates secretion of tracheobronchial tree, gastric glands, lacrimal glands, salivary glands, sweat glands. But biliary secretion and milk production is not affected .
16 VASCULAR ENDOTHELIUM: release of NO it leads to vasodilation of the vessels, leads to fall in blood pressure. It may also due to vasoconstriction action of Nor adrenaline is stopped by acetylcholine.
SMOOTH MUSCLE:
GIT: increased tone and peristaltic movement and relaxation of sphincters which leads to emptying of bowel contents and also produce cramps of the abdominal region.
BRONCHIAL MUSCLE:
Due to bronchoconstriction leads to difficulty in breathing,
GENITO URINARY TRACT:
In Ureter peristaltic movements is increased in Bladder due to relaxation of sphincters and contraction of detrusor smooth muscle leads to emptying of urine.
M4 RECEPTOR;3
LOCATION:
Brain and Heart
MECHANISM OF ACTION:
Similar to M2 receptor it has inhibitory signal through opening up of potassium channels and reduces Adenyl cyclase activity which leads to hyperpolarization of the membrane.
17 HEART:
Like M2 RECEPTOR it reduces the pacemaker activity ;conduction also slows down ; force of contraction of cardiac group of muscles also reduced.
BRAIN :
In particular areas of the brain leads to either stimulate or inhibition of neuro transmitter.
M5 RECEPTOR:3
LOCATION: Brain
MECHANISM OF ACTION:
Like M1 receptor it have stimulatory property of G protein coupled receptors, Gq.
BRAIN
It cause dopamine a neurotransmitter release which leads to reward behaviour.
NICOTINIC RECEPTOR:
It has two subtypes of receptor Nm and Nn type.
Nm TYPE; 3
LOCATION:
Neuromuscular junction.(muscle end plate)
18 MECHANISM OF ACTION: 3
It have pentameric like structure , ion channel which is present inside of it. They have intrinsic property. They have alpha 2, beta, epsilon, gamma, delta sub units present .Each subunit have four TM . After it gets activated leads to opening of these channels which cause inflow of cations results depolarization of the membrane and then Excitatory potential developed followed by action potential is produced. once AP is created leads to propagation of action potential to all the cell membranes.
AGONIST:
Nicotine
Phenyl trimethyl Ammonium
ANTAGONIST:
Alpha bungaro toxin,
Tubocurarine.
ACTION: contraction of skeletal muscles.
Nn RECEPTOR:3
LOCATION:
1. Autonomic ganglion cells 2. Adrenal medulla 3. Brain 4. Spinalcord
19 MECHANISM OF ACTION:
Like Nm receptor it also have intrinsic ion channel capacity, but it have only alpha and beta sub units.
AGONIST:
Nicotine
DMPP(Dimethyl phenyl piperazinium )
ANTAGONIST:
Trimethaphan
Hexamethonium
FUNCTIONS:
ADRENAL MEDULLA: it cause catecholamine release.
BRAIN:
Based on the areas of the brain it cause either stimulation or inhibition .
AUTONOMIC GANGLIA:
Both sympathetic and parasympathetic activation leads to impulse transmission.
ANTICHOLINESTERASE: 3
Anti-ChE are group of agents which prevents the breakdown of acetylcholine from hydrolysis, and it results produces cholinergic manifestations
20 CHEMISTRY:
Anti ChE are nothing but derivatives of either phosphoric acid group or carbamic group.
CLASSIFICATION: It can be classified into reversible and irreversible group.
In the irreversible group it can further sub divided into organophosphates and carbamates.
CARBAMATES: carbaryl (SEVIN); Propoxur (BAYGON).
REVERSIBLE GROUP: among the reversible group it is further classified into carba mates and acridine group of chemicals.
CARBAMATES:3
2. Neostigmine
4. Edrophonium
5. Rivastigmine
6. Donepezil
7. Galantamine.
ACRIDINE GROUP:
Tacrine.
21 MECHANISM OF ACTION; 3
The anticholinesterases act in the same mechanism of acetylcholine. The carbamates group cause carbamylation of the esteric site of the enzyme molecule. Similar to that organophosphates cause phosphorylation of that esteric site of the enzyme molecule.
Generally active region of anticholinesterases contains two sites one is anionic and another one esteric site. Esteric site is formed by amino acids like serine, glutamate, Histidine . anionic site is formed by aromatic amino acid group
Tryptophan.
ACETYLCHOLINE 3 is hydrolysed by positive charge group of ions gets attached to anionic site and nucleophilic attack on the esteric site leads to formation acetylated enzyme. Then acetylated form of enzyme reacts with water molecule to produce acetic acid and choline get released .Acetylated form of enzyme reacts very fast with water molecule leads to release of esteric site in free form with in few milli second. But the carbamylated form reaction will be slow, phosphorylated form of enzyme reaction will be extremely slow or it not undergoing any reaction at all.
Edrophonium, Tacrine gets attached to aromatic site only compared to organophosphates. Opc group of compounds gets attached to esteric site of the enzyme molecule. reactivation time of carbamylated enzyme is usually less time period than synthesis of new fresh enzyme molecule.
22 But in organophosphate group of phosphorylated enzyme reactivation time will be more compared to production of new enzyme molecule. The phosphorylated group of enzyme loss one of its alkyl group leads to development of resistant to hydrolysis which cause enzyme underwent Ageing process.
Most of the organophosphates group of compounds are lipid soluble in nature apart from Echothiophate.in carbamates nonpolar tertiary group mostly lipid solubility in nature and quarternatry group of compounds are highly water soluble.
STRUCTURE OF THE COMPOUND:7
Organophosphates compounds are called as esters of phosphoric acid chemicals. It consists of central phosphorus group of atom (P) and classical phosphoric (P=O) OR thiophosphoric bond (P=S).The symbol X denotes the leaving group which it was replaced by nucleophilic substitution of oxygen in the place of serine of AcHE.
23 The rate of Anticholinesterase inhibition was almost exclusively depends on the leaving group. If there is increased tendency to leaving results in high affinity to inhibition of that enzyme group.
These compounds can classified by their side chains and elements which attached to phosphorus atom. some of the organophosphates does not have anti
AcHE activity which cause low toxic to human beings. For example glyphosate and gluphosinate were used as herbicides, causing low toxicity to human beings.Monocrotophos,Dichlorvos10-18 belongs to phosphates group of organophosphates. Diazinon ,Fenthion, Parathion belonging to phosphorothioates (S=). Malathion 9, Dimethoate ,Disulfoton, Azinophos-ethyl, belongs to phosphorodithioates. nerve agents tabun ,sarin, soman, cyclosarin are comes under phosphonofluoridates. soman have four different isomeric forms
,(C+ P- ,C-P-,C+ P+ C-P+ ); VX it has two enantiomer said as P(+) ;P(-).It has differences in causing toxicity and AchE inhibition of rate of isomers in the nerve gas agents. people those who work in military setup are usually get exposed to this poison group during the period of war and general people usually get exposed to this nerve agents during the process of transportation and destruction period.
FLAME RETARDANTS:10
Several organophosphates used as fire retardants. The following compounds are Tris(2-chloroethyl )phosphate (TCEP); Tris (2-chloropropyl
24 )phosphate (TCPP); Tris (1,3 dichloroisopropyl)phosphate (TDCPP).These compounds cause heavy toxicity in aquatic group of organisms. but toxic to human beings less compared to marine group of organisms because of it does not have anti-AChE activity.
CARBAMATES:11
They are esters of carbamic acid. compared to organophosphates compounds structure of this group are not very complex like organophosphates
.It can be used as pesticides, medical treating conditions like alzheimers disease, myasthenia gravis etc. and in veterinary practice also used as a parasiticide.
CLASSIFICATION OF COMPOUNDS:19
Organophosphates can be classified by their chemical structure and toxicity which cause damage to organs.
DIMETHYL COMPOUNDS:
The following compounds are two methyl groups in their side chains.
1. Dichlorvas
2. Fenthion
3. Malathion.
4. Monocrotophos.
6. Dimethoate
7. Methyleparathion..
25 DIETHYL COMPOUNDS : They have two ethyl groups in their side chains.
1. Chlorpyrifos
2. Diazinon
3. Parathion –ethyl
4. Quinalphos.
5. Phorate
WHY THIS CLASSIFICATION NEEDED ? 19For dimethyl compounds anti cholinesterase ageing is very fast average around 3.7 hours compared to diethyl compounds have 31 hours ,so management for dimethyl compounds have to start as earlier.
WHO CLASSIFICATION:20
Based on the LD50 (mg/kg body weight ) it can be classified into five classes .The following are :
1. Extremely hazardous-oral <5;Dermal <50
2. Highly hazardous :oral :5-50; Dermal :50-200
3. Moderately hazardous: oral: 50-2000 ;Dermal :200-2000
4. Slightly hazardous: oral:>2000; Dermal :>2000
5. Unlikely to present acute : >5000 for both routes.
Based on the above classification compounds belongs to each class are as follows.
26 EXTREMELY HAZARDOUS:20 1. Aldicarb 2. Bromadiolone 3. Chlorethoxyfos 4. Chlormephos 5. Chlorophacinone 6. Diphacinone 7. Disulfoton 8. EPN 9. Ethorophos 10. Flocoumafen 11.Hexachlorobenzene 12. Mevinophos 13.Mercuric chloride 14.Parathion 15. Parathion methyl 16 Phenyl mercury acetate 17. Phorate 18. Phosphamidon 19. Sodium fluro acetate 20. Sulfotep 21.Tebuprimfos 22. Terbufos
2.HIGHLY HAZARDOUS:20 1. Acrolein 2. Allyl alcohol 3. Azinophos 4. Blasticidin 5. Butocarboxim
27 6. Cadusafos 7. Calcium arsenate 8. Carbofuran 9. Chlorfenvinphos 10. Coumaphos 11. Cyfluthrin 12. Beta cyfluthrin 13. Zeta cypermethrin 14. Dichlorvas 15. Dicrotophos 16. Dinoterb 17. Demeton s methyl 18. Edifenphos 19. Ethiofencarb 20. Famphur 21. Fenamiphos 22. Flucythrinate 23. Fluroacetamide 24. Formetanate 25. Furathiocarb 26. Heptenophos 27. Isoxathion 28. Lead arsenate 29. Mecarbam 30. Mercuric oxide 31. Methamidophos 32. Methiocarb 33. Monocrotophos 34. Nicotine 35. Omethoate
28 36. Paris Green 37. Pentachlrophenol 38. Propetamphos 39. Sodium Arsenite 40. Sodium Cyanide 41. Strychnine 42. Tefluthrin 43. Thallium Sulfate 44. Thiofanox 45. Thiometon 46. Vamidothion
3.MODERATELY TOXIC:20 1. Acephate 2. Bifenthrin 3. Chlorpyrifos 4. Cyhalothrin 5. Cypermethrin 6. Diazinon 7. Deltamethrin 8. Dimethoate 9. Endosulfan. 10. Fenthion 11. Glufosinate 12. Imidacloprid 13. Lambda-Cyhalothrin 14. Methasulfocarb 15. Permethrin 16. Profenofos 17. Propoxur
29 18. Pyrethrins 19. Quinalphos 20. Thiocloprid 21. Trichlorofon 22. Triflumizole 23. Xylylcarb 24. Ziram
4.SLIGHTLY HAZARDOUS;20 1. Borax 2. Clopyralid 3. Dichloran 4. Diuron 5. Ethephon 6. Halofenozide 7. Resmethrin 8. Pimaricin 9. Fosamine 10. Flamprop 11. Glyphosate 12. Malathion 13. Linuron 14. Fenarimol 15. Spinosad 16. Pyridate 17 Tetrachlorvinphos.
5.UNLIKELY TO CAUSE ACUTE POISON:20 1. Acrinathrin 2. Amitrole 3. Bifenox
30 4. Bromacil 5. Chlorfluazuron 6. Cycloprothrin 7. Dimethylpthalate 8. Ethofumesate 9. Fenfuram 10. Fluridone 11. Isoxaben 12. Nicosulfuron 13. Oxyflurofen 14. Propazine 15. Siduron 16. Transfluthrin 17. Zoxamide ABSORPTION: 21
Organophosphates can be absorbed in to our body through various routes like in the form of inhalation, ingestion, dermal route.
Rate of absorption depends on various factors like lipid solubility of the compounds, toxin bound time to our body, other associated any organic compounds ,integrity of the skin. because if there is already breach in the external layer there is increased chance of absorption.
Degree of absorption sometimes based on area of the skin involvement
.because some compounds are absorbed more readily via axillary region ,head and neck compared to hands.
31 DISTRIBUTION AND STORAGE:
Once it absorbed it get deposited in various tissues of our body like hepatic system, renal, adipose tissue areas. some of the compounds are lipid preference they get deposited released slowly it leads reappearance of clinical manifestation after recovery. Due to more lipid soluble nature of Opc compounds so it can able to cross the blood brain barrier system.
ELIMINATION:
The end products after gets metabolised in our body are excreted via renal system and to little extent via gastrointestinal system through faeces ,and respiratory system through exhalation process. Those compounds get deposited in adipose tissue it takes days to excrete compared to other compounds not deposited in fat within hours.
MECHANISM OF TOXICITY;22
Organophosphates compounds inactivate the enzyme acetyl cholinesterase which cause increased stasis of acetylcholine in the cholinergic synaptic places. first due to hydrolysis of organophosphate-enzyme complex leads to reactivation of enzyme can occur. But due to loss of one of the alkyl group reactivation cannot occur, instead of the Ageing process took place. once ageing process happened ,a fresh synthesis of new enzyme molecule is needed before function can be restored .increased acetylcholine leads to cholinergic manifestations can occur
32 CLINICAL FEATURES:
Based 23 on the route of exposure and the toxic agent, clinical onset of symptoms, severity and duration of symptoms can occur. After exposure to toxic organophosphates compounds the toxic manifestation will occur within 30 minutes to few hours. Dermal routes can takes place up to 12 hrs. sometimes may be delayed due to rate of absorption into the systemic circulation clinical features can be classified into following types;25-28
1. ACUTE CHOLINERGIC SYNDROME
2. INTERMEDIATE SYNDROME
3. ORGANOPHOSPHATE INDUCED DELAYED
POLYNEUROPATHY(OPIDP)
4. CHRONIC ORGANOPHOSPHATE INDUCED NEURO
PSYCHIATRIC DISORDER (COPIND).
ACUTE CHOLINERGIC SYNDROME:
Following exposure to organophosphates within few minutes clinical manifestations can occur in the form of nicotinic or muscarinic or central nervous system will develop.
MUSCARNIC MANIFESTATION:29
It is also known as WADIA type 1 syndrome.
33 RESPIRATORY SYSTEM:
Increased tracheobronchial secretions (bronchorrhoea);
Bronchoconstriction due to bronchial smooth muscle contraction.
CIRCULATORY SYSTEM :
Bradycardia; Hypotension.
Due to rate of impulse production from pacemaker cell SA node is reduced due to hyperpolarization of the cells.
In AV node and purkinje fibre system refractory period is prolonged which leads to conduction system of the heart gets slow down.
Due to force of contraction of atrial muscles are reduced and non uniform innervation by vagal nerves which leads conduction is different in atrial fibres
,then precipitate atrial arrhythmia in the form of atrial fibrillation or atrial flutter.
EYES: Due to contraction of circular muscle fibres of iris innervated by sphincter pupillae leads to pupillary constriction and produces classical
PINPPOINT PUPIL. lacrimal glands also get activated which leads to increased secretion from the eyes.
GASTROINTESTINAL SYSTEM:
Vomiting and profuse diarrhoea because of increased gastrointestinal movements.
GENITOURINARY SYSTEM:
Increased urination due to parasympathetic activation .
34 MOUTH: produces characteristic garlic odour and froth ,increased salivation due to activation of the salivary glands.
SWEAT GLANDS: Due to cholinergic activation sweating will develop
NICOTINIC MANIFESTATION:
SKELETAL MUSCLES: Due to lack of cholinesterase acetylcholine is not cleaved leads to binds same receptor as well as activate nearby receptor leads to continuous firing of pre junctional muscle fibres produces TWITCHING AND
FASICULATION.
Due to persistent depolarization of skeletal muscle end plates cause blockage in neuromuscular transmission of impulses leads to WEAKNESS and
PARALYSIS developed.
CIRCULATORY SYSTEM:
Tachycardia and Hypertension , due to sympathetic activation and release of catechol amines.
RESPIRATORY SYSTEM:
Reduced ventilation and respiratory muscle weakness cause respiratory failure.
35 3.CENTRAL NERVOUS SYSTEM EFFECTS:
1) Ataxia
2) Convulsions
3) Coma
4) Anxiety
5) Tremors
6) Insomnia
7) Restlessness
8) Dysarthria .
9) Reflexes are absent.
36 2.INTERMEDIATE SYNDROME:30
The syndrome is first identified during the period of 1987 by karalliedde and senanayake.
WHY IT WAS NAMED AS INTERMEDIATE SYNDROME ?
Because it usually develops after the Acute cholinergic syndrome before organophosphate induced polyneuropathy so its was intermediate between the two syndromes.
The intermediate syndrome was present approximately around 20% patients following exposure to organophosphates. It doesn’t have clear association between specific organophosphates and development of syndrome.
PATHOPHYSIOLOGY :
Due to prolonged effect of nicotinic action , primary motor end plate degeneration
ONSET OF TIME:
The syndrome normally developed two to four days after exposure to toxic compounds and the signs of acute cholinergic syndrome like muscle fasciculation, muscarinic signs are no longer seen.
CHARACTERSTIC FEATURES:
One of the most important features are weakness of the respiratory muscles (diaphragm, intercostal muscles, neck muscles ,accessory muscles of
37 respiration ) proximal group of muscles in limbs. But sometimes some of the muscles innervated by cranial nerves also get affected. In proximal group also mainly shoulder abductors and hip flexors group are affected. sensory system usually intact, DTR are absent/diminished.
The degree and extent of muscle weakness it may varied following the development of the syndrome. Some patients developed neck muscles only, some people developed only weakness of the proximal group of the muscles.
Those patients with proximal muscle weakness of the limbs needs careful observation to look for any respiratory function is compromised or not.
MANAGEMENT:
Ventilator care is the main supportive treatment, if there is any delay in instituting ventilator care patient will land up in death. During the period of ventilator support patient needs low dose of non depolarizing muscle relaxant.
Succinylcholine , group of depolarizing muscle relaxant are contraindicated.
DURATION:
The duration of ventilator care usually varies it needs around 7-15 days some times even up to 21 days are needed.
Weaning from ventilator is carried by stage by stage procedure, before weaning patients needs continuous positive airway pressure. continuous monitoring of respiratory function in the form of ARTERIAL BLOOD GAS
38 analysis to check partial pressure of oxygen and carbon dioxide , arterial oxygen saturation and Acid base balance status of the body
Monitoring of fluids and electrolytes are also needed due to their GI
LOSS. prophylatic antibiotics is not needed unless there is evidence of aspiration pneumonitis .maintenance of nutrition, prevention of pressure sores, and other supportive measures should take during the period of ventilator support. normally patients will recover without any sequeale. role of oximes is not certain.
Randomised trials are required to study about the efficacy of oximes In intermediate syndrome.one more important is electrophysiological studies
DECREMENTING RESPONSE. It is defined as continued reduction in twitch height and compound muscle action potential with repetitive stimulation.
ORGANOPHOSPHATE INDUCED POLY NEUROPATHY:31-34
It is delayed and rare neurological manifestation.
ONSET OF TIME:
Mostly it developed after two to three weeks following exposure.
PATHOPHYSIOLOGY:
Mostly it is due to inhibition of enzymes other than acetylcholine esterase also and slow release of organophosphates released from the body fat storage sites.
39 CHARACTERSTIC FEATURE:
Mostly it is due to some organophosphates like triortho cresylphosphate
,but it was not so much common in agents like nerve gas.. It is both motor and sensory nerve involvement especially long myelinated nerve fibres are more commonly affected.
CLINICAL FEATURES:
It can be divided into motor manifestation and sensory manifestation.
MOTOR MANIFESTATION:
1. Cramp like pain especially calf muscle group.
2. Acute flaccid paralysis initially involved lower limbs followed by
upper limbs .
3. Paraplegia progressed to quadriplegia
4. Wrist and foot drop
5. Gait disturbances initially high stepping gait and followed by
shuffling gait in later.
6. Mild pyramidal signs may be present in the form of spasticity.
7. Tendon reflexes are reduced or lost.
SENSORY MANIFESTATION:
1. Glove and stocking sensation peripheral neuropathy.
40 CHRONIC ORGANOPHOSPHATE INDUCED NEURO-PSYCHIATRY
DISORDER;(COPIND)31-34
Chronic low dose exposure to organophosphate compounds, minimum forty hours per week and nine month per year. It had no cholinergic manifestation.
NEUROLOGICAL MANIFESTATION:
1. Memory impairment
2. Concentration impairment
3. learning impairment
4. Chronic fatigue syndrome
5. Parkinson like extrapyramidal manifestation like resting tremor;
brady kinesia; rigidity of the limbs ,postural hypotension, dystonia.
NOTE:
These Parkinson like manifestation will not response to levodopa.
PSYCHIATRIC MANIFESTATION:
1. Anxiety
2. Depression
3. Dysthmia
Plasma cholinesterase will be normal in the above disorder.
41 DELAYED ORGANOPHOSPHATE ENCEPHALOPATHY (DOPE):
It is also known as CNS intermediate, new syndrome. it was recently recognised and described in the year 2008.
CLINICAL FEATURES:
1. Normal sensorium then progression to coma days after poisoning
(delayed coma)
2. Miotic pupils which is not reacting in nature.
3. Extrapyramidal signs-choreo athetosis; cog wheel rigidity; dystonia;
INVESTIGATION:
1. CT Brain plain and CSF analysis were normal study.
2. EEG:bi hemispheric slow waves showed it was consistent with
encephalopathy.
3. Pseudocholinesterases level will be low.
MANAGEMENT:
Requirement of Atropine dose should increase and supportive treatment
PROGNOSIS:
Good if proper supportive care given.
OTHER SYSTEMIC EFFECTS DUE TO TOXICITY:
IMMUNITY: There is alteration in the immunity of patients those who are exposed to toxin produce fall in the immunity levels cause immunosuppressive effects.
42 REPRODUCTIVE SYSTEM:34
Most of the studies shows organophosphates induce alteration in the reproductive functions through impairment of Hypothalamo -pituitary-gonadal axis suppression.one more mechanism for the anti gonadal effects due to suppression of the steroid hormone synthesis. Recurrent exposure to Opc compound dimethoate34 leads to serum testosterone levels are reduced, as well as size of the testicles and sperm motility also gets reduced, increased number of abnormal sperms cause infertility. sub lethal dose of quinalphos 35 also cause severe suppression of spermatogenesis process. Dimethoate mainly blocks the rate limiting step of steroid genesis and produces infertility .
RENAL SYSTEM:
Acute kidney injury36 is very rare seen. various mechanism cause acute kidney injury are oxidative stress ,renal tubular damage ,rhabdomyolysis, hypovolemia followed by dehydration.
CARDIOVASCULAR SYSTEM:
Hypoxemia, Electrolyte disturbances, acidosis precipitates cardiovascular manifestation of those who exposed to organophosphate.
Non cardiogenic pulmonary edema, hypertension as well as hypotension,electrocardiographic37 abnormalities in the form of prolonged QT interval, ST-T changes ,conduction blocks, sinus tachycardia, sinus bradycardia,
43 ventricular fibrillation, Torsade de pointes type, polymorphic ventricular tachycardia
Intensive management of supporting care and adequate dose of Atropine very early during the period of admission cause reduction in mortality rate.
HEPATOBILIARY SYSTEM:
Due to organophosphates gets metabolized in the liver produces Fatty change, necrosis 38 of the liver cell particularly in the centri lobular region as well as dilation of sinusoidal region.
GASTROINTESTINAL SYSTEM:
Following ingestion of organophosphates produces39 edema
,circumferential hyperemia, sometimes bleeding points spots also noticed in the oesophageal region.
ORGANOPHOSPHATES IN ANTENATAL MOTHER:
Earlier during the first trimester of pregnancy it produces abortions as well as congenital defects40 like limb defects, bony deformities, cleft palate and poly dactly second and third trimester poisoning if there is effective management done there will be no foetal loss.
OXIDATIVE STRESS:
After exposure to toxic compounds there will be lipid peroxidation 41 of the membranes, antioxidants substance glutathione levels will be reduced, so there is increased oxidative stress.
44 SKELETAL MUSCLE SYSTEM:
Due to toxins it produce myopathy, as well as muscle necrosis which leads to patient developed muscle weakness. there is disruption of Z bands42 in the sarcoplasmic reticulum. After toxicity tetanic stimulation of the normal muscle not able to maintain.
SEVERITY ASSESMENT:
BARDIN CLASSIFICATION43: Based on the clinical manifestations it can be graded as follows.
GRADE 0 : No manifestation
GRADE 1 : Patient is conscious, muscular fasciculation ,increased
secretions.
GRADE 2 : Patient had lost their consciousness, hypotension
developed along with grade 1 features.
GRADE 3 : Patient is stuporous, CXR will be abnormal ,partial
pressure of oxygen will be less than 10 mm hg along
with grade 2 features.
PARADENIAYA SEVERITY ASSESEMENT SCORE:
The following parameters are used to asses the severity after exposure to opc poisoning:
1. Pupil size: >2mm -0 ;<2mm-1; pinpoint-2
2. Fasiculations: No-0; not generalized or continuos:1; generalized or
continuos:2
45 3. Respiratory rate: <20 -0; >20-1; >20 along with central cyanosis-2
4. Heart rate:>60 -0; 40-60:1 <40 :2
5. Level of consciousness:conscious-0 ;impaired but respond to oral
commands:1;those who not responds to oral commands:2 ;if seizure
present add one more point.
CLINICAL SEVERITY GRADING:
Based on the RBC cholinesterase level, muscarinic ,nicotinic, and CNS manifestations. It can be classified into mild ,moderate, severe category.
MILD TYPE:
RBC CHOLINESTERASES LEVEL: More than 40 %
MUSCARINIC SYMPTOMS:
Vomiting, diarrhoea, salivation, bronchorrhoea, bronchoconstriction,
bradycardia.
NICOTINIC : No manifestation
CNS: Headache and Dizziness.
MODERATE :
RBC CHOLINESTERASES LEVEL: 20-40%
MUSCARINIC: miosis, in addition to mild type symptoms also.
NICOTINIC: fasciculation(fine group of muscles )
CNS: Ataxia; Dysarthria and also mild category type of symptoms.
46 SEVERE: RBC CHOLINESTERASES LEVEL : Less than 20%
MUSCARINIC: No symptoms
NICOTINIC: fasciculation involved diaphragm and respiratory group of muscles.
CNS: coma and convulsions in addition moderate type category of symptoms.
DIAGNOSIS:
Organophosphate poisoning is mainly clinical diagnosis but some of the laboratory parameters are used to confirm the patient exposed to toxic compound or not. The following points are used
1. By History patient exposed to toxic substance can identify.
2. Clinical symptoms and signs
3. After treatment with anticholinergic drugs like atropine, glycopyrrolate
and oximes patient symptoms and signs will improve.
4. Cholinesterase level in the blood.
First foremost important point in diagnosing opc poisoning by clinical
history. sometimes we can ask the patient attenders to bring the container
to identify patients is exposed to opc compound or some other pesticides.
organophosphate poisoning have characteristic smell garlic like odour will
present. Through gastric aspirate sample ,skin, organophosphate
compounds can identified through chromatography technique .some times
47 metabolites of organophosphates compounds are detected using gastric
lavage samples, urine, blood. second clinical signs and symptoms is
specific to organophosphates are detected like froth from the mouth,
pupillary changes ,on auscultation crackles will be present, pulse rate
shows bradycardia or tachycardia, blood pressure either hypotension or
hypertension fasciculation and bedside clinical assessment of neck
muscle weakness in the form of lifting the head from the bed and how
many seconds are able to maintain.
ATROPINE TEST: inject 0.6-1.2 mg of atropine intravenously if the patient pulse rate rises 25/minute and if they developed skin flushing we can diagnose patient had either no toxicity or only minimal toxicity.
CHOLINESTERASE LEVEL:Normally44 there will be decrease in the cholinesterase level if toxicity developed in our body. generally RBC cholinesterase level measurement is more accurate than plasma level measurement .plasma cholinesterase have some advantages, it is easy to available
;and also very easy to measure; useful in acutely exposed persons. usually fifty percentage reduction from the normal values and followed progressive increase after successful treatment .It is also used to monitor the clinical course, if the values are persistently low can prediction of intermediate syndrome. In case of severe poisoning plasma cholinesterase level comes to normal level by minimum three to four weeks, but for RBC cholinesterase it takes around more than five weeks if the oximes are not administrated.
48 OTHER PARAMETERS TO HELP IN DIAGNOSE:
COMPLETE BLOOD COUNT: 44
They will have neutrophilic leucocytosis
RENAL FUNCTION TEST:
Patient will have transient hyper glycemia and glycosuria.It is due to stimulation of the adrenal gland, release of catechol amines, oxidative stress and renal tubular damage. patient will also developed Hypokalemia.
SERUM LEVELS :organophosphates compounds their serum level and their metabolites also measured .
SERUM AMYLASE: Increased serum amylase45-48 levels usually correlate with severity as well as presence of shock. It is due to cholinergic stimulation of salivary and pancreatic glands and rarely due to acute pancreatitis.
CPK LEVELS AND LIVER FUNCTION TEST:
Increased serum cpk levels and liver enzymes also helps in diagnosing it.
CHEST XRAY: if patient developed aspiration it can be helpful.
ELECTROCARDIOGRAM:
various ECG changes will be present like sinus tachycardia, sinus bradycardia, arrthymia, PROLONGED QT INTERVAL.one of the poor prognostic factors in organophosphate poisoning is prolonged QT interval.it is due to oxidative stress cause conduction problems in the form of negative ionotrophy and chronotrophic effects.
49 ARTERIAL BLOOD GAS ANALYSIS:
Metabolic acidosis developed in patients those who are presented with hypotension. Low pH also predicts mortality in both carbamates and organophosphate poisoning. Sodium bicarbonate therapy is useful for treating these patients.
URINE ROUTINE:
Proteinuria, glycosuria will present. sometimes metabolites of organophosphates are measured in the urine.
ULTRASOUND OF ABDOMEN:
To look for pancreas appears whether it is normal or inflamed .
ELECTROPHYSIOLOGICAL STUDIES:49
In organophosphates poisoning there will be three specific characteristic
seen. They are
1. There will be repetitive firing following a single stimulus.it is mostly
observed in acute cholinergic syndrome.
2. DECREMENT-INCREMENT response: With repetitive nerve
stimulus there will be gradual reduction in height of the twitching or
compound muscle action potential followed by their increase in
response.
3. DECREMENTING RESPONSE: As previously mentioned in
intermediate syndrome patients will show there will be Decrementing
response by 30 HZ nerve stimulation.
50
TREATMENT OF ORGANOPHOSPHATE POISONING:
Four basic principles is used to treat the opc patients.
1. Identification of the poison
2. Reduce further absorption of toxins into our body.
3. Enhancing the elimination of toxins.
4. Neutralizations of the toxins.
IDENTIFICATION OF THE POISON:
Poison can be identified by as previously discussed
1. History by patient themselves or patient attenders.
2. Through clinical presentation.
3. To show photographs and
4. WHO colour code in the container.
51 WHO COLOUR CODE: WHO categorize the toxic substance by using colour code systems
RED :
Extremely TOXIC substances. Examples; Monocrotophos, ethylmercuric
acetate Etc..
YELLOW:
Highly toxic substance .Examples; Endosulfan;carbaryl,etc…
BLUE :
Moderately toxic. Examples: Malathion,glyphosate,etc..
GREEN :
Slightly toxic. Example :Mancozeb, oxyflurofen.etc…
ACUTE CHOLINERGIC CRISIS TREATMENT:50
ABSORPTION OF TOXINS: To reduce absorption of toxins by various methods like Decontamination procedure should take care.
DECONTAMINATION :
First health care workers should take necessary personal protection to prevent from exposure of toxic substances. PPE should not contain latex/vinyl of these materials. All the clothes patient wearing should remove wash with soap and water. usually soaps 30% ethanol contains can used. Ocular decontamination through water/normal saline.
52 STABILISATION: Airway, circulation, breathing should patent.
PATIENT POSITION: patient should be in left lateral position, withneck extension.so that it can reduce the chances of aspiration, airway becomes patent, decreases the gastric pyloric emptying and then prevent the absorption of the toxins.
.GASTROINTESTINAL DECONTAMINATION:
GASTRIC LAVAGE: It is one of the first foremost intervention is needed for the patient, usually it decreases the absorption of toxin by 42% within
20 minutes ,and only 16% if done within one hour presented to hospital. mostly it is done in co operative and conscious patients only. Recommended fluid is used for lavage is Tap water ,5-10 ml/kg. There is also no evidence if large tube is used is better for lavage procedures.
EMESIS: Emesis is induced by Ipecacuanha is contraindicated for organophosphte poisoning .
ACTIVATED CHARCOAL:
Recent update in treatment of organophosphate poisoning is using activated charcoal does not the support for treating cases, but also shows there is no evidence for harmful to patients.
2. NEUTRALISATION OF TOXINS BY USING ANTIDOTES:
Next step in treatment after reducing the absorption of toxins to reduce the clinical symptoms and signs by using specific antidote to combat the toxicity.
53 The antidote of choice is anticholinergic medication is ATROPINE, sometimes
Glycopyrrolate is also used.
ATROPINE:
BIOCHEMISTRY:
Natural alkaloids belonging to solanaceae family.It has two isomeric forms. Levo isomers are active compared to Dextro isomers. It is racemic in nature. Source of origin is Atropa belladonna, Datura stramonium.
ABSORPTION:
It is absorbed in the gastrointestinal tract. It has capacity to penetrate the cornea after applied into eyes.
METABOLISM AND EXCRETION:
Almost fifty percentage of drugs are get first pass metabolism in the liver have half life around 3-4 hours and remaining is excreted unchanged form through urine.
MECHANISM OF ACTION:
It is competitive antagonist for acetylcholine and block muscarinic syndromes.
VARIOUS REGIMEN FORMS:50-52
Generally for treating opc patients there is two different modalities using atropine for neutralization.one is BOLUS DOSE regimen and another is
INCREMENTAL DOSE regimen.
54 BOLUS DOSE REGIMEN:
2- 5 mg of atropine every 10-15 minutes followed by maintenance infusion by using reduced doses .
INCREMENTAL DOSE REGIMEN :
1.8 TO 3 mg intravenous of atropine and double the dose every five minutes by clinical assessing and continue till the signs of atropinization occurs followed by 10- 20 % of dose required for atropinization is used as maintenance dose as a continuous infusion hourly. Incremental dose is superior regimen compared to bolus regimen to treat the patients.
AIM OF THERPHY:
1. To reversal of cholinergic manifestation
2. To improve the functions of respiratory system and cardiovascular
system.
TARGENT POINTS:
1. One of the most reliable features of atropinzation is clear lungs on
auscultation.
2. Systolic blood pressure should maintain above 90 mmHg.
3. Axillary region should be dry.
4. Bowel sounds just present
5. Pupill no more pinpoint in nature.
55 TARGET ON SUBSEQUENT DAYS:
DAY 2: HR: more than 100 per minute.
DAY 3:HR: more than 90 per minute
Subsequent days maintain minimum 80 beats per minute.
ATROPINE CHART:
The following parameters are used to assess the adequate dose of atropine.
1. Time
2. Heart rate
3. Clear lungs
4. Pupil
5. Dry axilla
6. Systolic blood pressure > 90 mmHg
7. Bowel sounds
8. Mental state
9. Fever more than 37.5 degree
10. Oxygen saturation spo2
11. Atropine infusion dose.
Patient needs to be reassessed every 5 minutes to check whether dose is adequate or not.
If there is reappearance of clinical manifestation dose should be doubled.
Once adequate parameters are reached patient should monitor for hourly for next six hours to see the efficacy of infusion rate.
56 ATROPINE TOXICITY:
Bowel sounds are absent, fever, confusional state indicates atropine toxicity.
MANAGEMENT:
Stop the infusion for one hour. After the temperature comes down and patient becomes calm restart the infusion 80% of the initial infusion rate. Usually not more than three to five mg per hour of infusion rate is not needed. After the patients vitals stable infusion is reduced to 20% every fourth hourly and then stop.
GLYCOPYRROLATE:51
Like atropine is used to control secretions of the patients, but it have some advantages like tachycardia is not so much, proper control of secretions, CNS manifestation not present due to not able to cross the blood brain barrier.
REACTIVATION OF ACETYLCHOLINESTERASES BY OXIMES:
Oximes are used to activation of cholinesterase inhibited by organophosphates poisoning. It was discovered by Wilson 1950.various types are available obidoxime, trimedoxime, pralidoxime.
Among these Pralidoxime are most commonly used. Generally oximes are present in four different forms are chloride,iodide, metilsulfate, mesilate.In most of the developing countries chloride and iodide forms are used.
Compared to iodide, chloride have certain advantages like no thyroid toxicity, more active compound present in the per gram of salt.
57 MECHANISM OF ACTION;53
1. Through nucleo phillic and detoxification attack in the phosphorylated
form of enzymes removed the phosphate group and restores the acetyl
cholinesterase activity.
2. Detoxification of the unbound toxin molecules
3 Endogenously Anticholinergic effects are present .
THERAPEUTIC EFFECTIVENESS:
Oximes its therapeutic effectiveness are depends on various reasons.
1 Concentration of the toxic compound ingested by patient(poison load)
2. Time lapse between poison consumption and administration of oximes.
3. Type of the organophosphate compound ,due to dimethyl compounds
aging at slower rate so diethyl compounds are more effectively used.
4. Lipid solubility of organophosphate compound
5. Concentration of oximes in blood.
DOSING:
PAM :one to three grams(1-3 gm/ day),for effective treatment serum levels should maintain more than four milligram per litre(>4mg/lit).It has no role after 48 hours.
BOLUS:20-40 mg/kg followed by continuos infusion at rate of 500 mg per hour infusion.
WHO RECOMMENDATION:
30mg/kg bolus followed by infusion of 8mg/kg/hour infusion .
58 END POINT:
The following therapeutic end points are used
1. Recovery from muscle fasciculation and weakness, Reactivation and
increment in the serum cholinesterase level.
2. If un aged organophosphates are released from fatty tissue use longer
than 24 hours.
3. Infusion should continue till from symptom free or atleast 12 hours
without additional atropine or until extubation.
SIDE EFFECTS:
Dizziness, headache ,blurred vision, double vision. Rapid administration can produce laryngospasm, tachycardia, muscular spasm, transient neuromuscular blockade.
INFERENCE:
However, current evidence shows oximes are neither harmful nor beneficial. Not useful in case of severe poisoning .WHO recommendation regimen is not supported. Therefore RCT are further required to examine other strategies and regimens.
CARDIOVASCULAR COMPLICATIONS:
Normally due to muscarinic receptor activity it produces bradycardia and hypotension, it responds to atropine. sometimes severe hypotension can benefit by using of inotrophic agents.
59 RESPIRATORY COMPLICATION:
All patients with respiratory distress should give oxygen therapy. Some of the indications for ventilator support. 1.Respiratory gas tensions :
Direct indices: Arterial oxygen tension < 50mm Hg on room air
;Arterial Co2 tension > 50 mm Hg in the absence of metabolic
alkalosis.
Derived indices: PA-aOo2 > 350 mm Hg ;Pa o2/Fio2 < 250 mmHg
2.Clinical:
Respiratory rate is more than 35 breaths/minute.
3.Mechanical indices:
Vital capacity <15 ml/kg. ;Maximum inspiratory force < 25 cm of
water.
WEANING OFF VENTILATOR SUPPORT:
Before weaning any patient from ventilator asses respiratory muscle function.
Reduce gradually from pressure support level in CPAP mode. Extubate the patient if spontaneous respiration present without distress and tidal volume of more than 5ml/kg at a pressure of 3-5 cm of water.
NEUROLOGICAL COMPLICATIONS:
Patient with organophosphates poisoning are frequently developed delirium. It is due to by toxic compound, atropine toxicity, hypoxia, along with alcohol ingested. DIAZEPAM 54 are most commonly used as first line therapy for
60 seizures. usually seizures are more common in nerve gas agents like tabun, soman.
Most of the opioids are metabolized through serum cholinesterase level, so it use for sedation in case of pulmonary edema can worsen CNS complications. PHENYTOIN not recommended for controlling seizures due to membrane stabilizing property .Seizures are mostly not seen in well oxygenated patients.
DOSE: 10 MG slow iv it can be repeated till 30-40 mg/24 hrs. GACYCLIDINE :55 Anti glutamate compound inhibits seizure caused by nerve gas agents.
MAGNESIUM SULPHATE:
It blocks calcium channels and reduce release of acetylcholine from presynaptic terminals. It reduces the CNS over stimulation from due to activation of NMDA receptor. It decreases the hospital staying time and mortality.
CLONIDINE:57
Centrally acting alpha 2 receptor agonist, due to inhibition of presynaptic acetylcholine release. It have synergistic action with atropine.
DOSE: Bolus injection (0.15- 0.30 mg ) followed by continuous infusion
of at the rate of 0.5 mg /24 hours.
KETAMINE:
Non competitive antagonist of NMDA receptor within one hour of nerve gas agents induced seizures along with diazepam.
61 TEZAMPANEL:
Glutamate receptor antagonist especially for kainate receptor is useful in nerve gas agent induced seizures and neuropathy.
PROTEASE INHIBITOR:
It prevents delayed neuropathy.
ANTIOXIDANTS: Lipid peroxidation caused by organophosphate poisoning so antioxidants can be used. Vitamin E reported have therapeutic effect.
OPIDN: In case of organophosphate induced delayed neuropathy corticosteroids are used.
SODIUM BICARBONATE;58
Infusion of sodium bicarbonate are useful in case of nerve gas agent poisoning.
DOSE: 5Meq/kg in one hour followed by 5-6mEQ/kg/day
EARLY ENTERAL FEEDING:
Due to prevention of entero hepatic circulation early enteral feeding showed improvement in sick patients. Also nutritional supplementation very early is needed because these patients require prolonged ventilator support.
FRESH FROZEN PLASMA:56
Currently, have no clear evidence in opc patients.
Removal of organophosphates from blood using hemodilution
,hemofiltration and hemodialysis need further research. use of recombinant bacterial phosphotriesterases or hydrolases break down opc by enzymatically.
62 MATERIALS AND METHODS:
SOURCE DATA:
Cases admitted in emergency ward, medicine ward, intensive care unit in
Government mohan kumaramangalam medical college and Hospital –salem.
STUDY DESIGN:
Cross sectional prospective study
PERIOD OF STUDY:
The study was conducted from February 2018 to November 2019
ETHICS COMMITTEE APPROVAL:
Approval was obtained from Institutional ethics committee
INCLUSION CRITERIA:
Patient with history of organophosphorus poisoning with clinical features and physical evidence of poisoning were study subjects.
EXCLUSION CRITERIA:
1. Patients those who consumed entirely different poison from opc
2. Patients those who are chronic alcoholics
3. Patients with history suggestive of gallstone diseases
4. Drug history,Eg: Thiazides,furosemide,mercaptopurine,Azathioprine.
63 SAMPLE COLLECTION:
From all selected patients about 3ml of venous blood were collected on two occasions, first sample within 24 hours of consumption of poison (sample-1) and next after 24 hours of the first sample(sample-2).The samples was centrifuged at 3000 rpm for 15 minutes, then serum was separated and allowed to froze .serum amylase was estimated by using auto analyser CNP-G3 method. other lab investigations like renal function test, liver function test, was also analysed. clinical parameters was also analysed like pupil size, pulse, RR, secretions, sensorium of the patients using POP scale.
STATISTICAL ANALYSIS:
All the collected data were statistically analysed using appropriate statistical value.
64 OBSERVATION AND RESULTS:
Age group
Frequency Percent
<20 8 8.0%
21-30 27 27.0%
31-40 36 36.0%
Valid 41-50 12 12.0%
51-60 10 10.0%
>61 7 7.0%
Total 100 100.0% .
40 36 35
30 27
25
20 Frequency 15 12 10 10 8 7 5
0 <20 21-30 31-40 41-50 51-60 >61
In our study most common age group is affected is between 31-40 years followed by 21-30 years of age.
65 Gender
Frequency Percent
Male 69 69.0%
Valid Female 31 31.0%
Total 100 100.0%
Female 31%
Male 69%
Majority of patients in our study are male(69%) compared to females 31%
66 Compound
Frequency Percent
DIAZINON 5 5.0%
DICHLORIVAS 14 14.0%
DIMETHOATE 16 16.0%
DIMETHOATE 2 2.0%
FOLIDOL 8 8.0% Valid MALATHION 12 12.0%
MONOCROTOPHOS 22 22.0%
PHORATE 17 17.0%
TRIAZOPHOS 4 4.0%
Total 100 100.0%
TRIAZOPHOS 4 PHORATE 17 MONOCROTOPHOS 22 MALATHION 12 FOLIDOL 8 DIMETHOATE 2
DIMETHOATE 16 DICHLORIVAS 14 DIAZINON 5
0 5 10 15 20 25 Frequency
Most compound consumed in our study is Monocrotophos (22%) followed by phorate(17%)..
67
VENTILATOR SUPPORT NEEDED
Frequency Percent
No 68 68.0%
Valid Yes 32 32.0%
Total 100 100.0%
Yes 32%
No 68%
In our study 68 patients does not require ventilator support ;32 patients need ventilator
68
OUTCOME
Frequency Percent
Alive 83 83.0%
Valid Dead 17 17.0%
Total 100 100.0%
Dead 17%
Alive 83%
Out of 100 patients in our study 83 patients are alive and 17 patients dead.
69 MIOSIS Frequency Percent
>2mm 50 50.0%
<2mm 34 34.0% Valid Pin Point 16 16.0%
Total 100 100.0%
60
50 50
40
34
30 Frequency
20 16
10
0 >2mm <2mm Pin Point
In our study majority of people shows pupil size more than
2mm(50),pinpoint pupil present in 16 patients.
.
70 FASICULATION
Frequency Percent
None 63 63.0%
Present, 25 25.0% Generalised/Continuous Valid Both Generalised and 12 12.0% Continuous
Total 100 100.0%
Both Generalised and Continious 12
Present, Generalised/Continious 25
None 63
0 10 20 30 40 50 60 70 Frequency
63 patients in our study does not show any fasiculations;12 patients have both generalized and continuous fasciculation.
71 Heart rate
Frequency Percent
>60 51 51.0
41-60 32 32.0 Valid <40 17 17.0
Total 100 100.0
60
51 50
40
32 30 Frequency
20 17
10
0 >60 41-60 <40
51 patients have normal heart rate;17 patients have severe bradycardia .
72 RESPIRATORY FAILURE
Frequency Percent
<20/min 68 68.0%
>20/min 1 1.0% Valid >20/min with cyanosis 31 31.0%
Total 100 100.0%
80
70 68
60
50
40 31 Frequency 30
20
10 1 0 <20/min >20/min >20/min with cyanosis
68 patients in our study have normal respiratory rate;32 patients have
Tachypneic.
73 DEPRESSED MENTAL STATUS
Frequency Percent
Conscious and rationale 58 58.0%
Impaired response to verbal 30 30.0% commands Valid No reponse to verbal commands 12 12.0%
Total 100 100.0%
No reponse to verbal commands 12
Impaired response to verbal commands 30
Conscious and rationale 58
0 10 20 30 40 50 60 70 Frequency
58 patients in our study have normal sensorium ;12 patients not responds to oral commands.
74 SEIZURES
Frequency Percent
Absent 92 92.0%
Valid Present 8 8.0%
Total 100 100.0%
Present 8%
Absent 92%
Out of 100 patients in our study only 8 patients developed convulsions remaining all patients had no episode of seizures.
75 POP SCORE SEVERITY
Frequency Percent
Normal 39 39.0%
Mild 29 29.0%
Valid Moderate 15 15.0%
Severe 17 17.0%
Total 100 100.0%
45 39 40
35 29 30
25
20 17 Frequency 15 15
10
5
0 Normal Mild Moderate Severe
39 patients in our study normal;29 patients have mild category;17 have severe..
76 SERUM AMYLASE Std. Miosis N Mean P value (DAY 1) Deviation
>2mm 50 137.64 48.06
<2mm 34 272.18 93.96
Pin <0.0001 16 460.00 65.41 Point
Total 100 234.96 134.83
600.00
500.00 460.00
400.00
300.00 272.18
200.00 137.64
100.00
0.00 >2mm <2mm Pin Point
50 patients have pupil size >2mm have serum amylase on day 1is 137.64 compared to pinpoint is 460 IU/L.
77
Std. Mea Miosis N Deviatio P value n n SERUM AMYLASE >2mm 50 38.72 8.91 (DAY 2) <0.000 <2mm 34 59.71 13.53 1 Pin Point 16 75.25 13.62
Total 100 51.70 18.03
100.00 90.00 80.00 75.25 70.00 59.71 60.00 50.00 38.72 40.00 30.00 20.00 10.00 0.00 >2mm <2mm Pin Point
On day 2 due to treatment serum amylase is reduced. pupil size > 2mm is
38.72; pinpoint pupil have serum amylase is 75.25.
78 Descriptives
Std. FASICULATION N Mean P value Deviation
None 63 154.83 60.21
Present, 25 316.08 100.26 SERUM Generalised/Continuous AMYLASE <0.0001 Both Generalised and (DAY1) 12 486.67 19.71 Continuous
Total 100 234.96 134.83
Both Generalised and Continious 486.67
Present, Generalised/Continious 316.08
None 154.83
0.00 100.00 200.00 300.00 400.00 500.00 600.00
63 patients who does not develop fasciculation have serum amylase is
154.83; 12 patients with fasciculation have 486.67…
79
Std. FASICULATION N Mean P value Deviation
None 63 41.21 10.42
Present, Generalised/ 25 67.04 14.57 SERUM Continuous AMYLASE <0.0001 Both Generalised and (DAY 2) 12 74.83 10.07 Continuous Total 100 51.70 18.03
Both Generalised and 74.83 Continious
Present, 67.04 Generalised/Continious
None 41.21
0.00 20.00 40.00 60.00 80.00 100.00
On day 2 amylase values are reduced 41.21 in normal patients and 74.83
IU/L in fasciculation developed patients.
80
Mean Dependent Variable Difference P value (I-J) Present, Generalised/Continuo -161.25460* <0.0001 None us Both Generalised and -331.84127* <0.0001 Continuous SERUM * Present, None 161.25460 <0.0001 AMYLAS Generalised/ Both Generalised and E (DAY1) -170.58667* <0.0001 Continuous Continuous None 331.84127* <0.0001 Both Present, Generalised and Generalised/Continuo 170.58667* <0.0001 Continuous us Present, Generalised/Continuo -25.83365* <0.0001 None us Both Generalised and -33.62698* <0.0001 SERUM Continuous AMYLAS Present, None 25.83365* <0.0001 E (DAY Generalised/ Both Generalised and -7.79333 .173 2) Continuous Continuous None 33.62698* <0.0001 Both Present, Generalised and Generalised/Continuo 7.79333 .173 Continuous us
81
Heart Std. N Mean P value Rate Deviation
>60 51 141.45 55.72
SERUM 41-60 32 251.94 62.02 AMYLASE <0.0001 (DAY1) <40 17 483.53 35.05
Total 100 234.96 134.83
600.00
500.00 483.53
400.00
300.00 251.94
200.00 141.45
100.00
0.00 >60 41-60 <40
51 patients with normal heart rate have serum amylase is 141.45 compared to 483.53 in patients with severe bradycardia on day 1.
82
Heart Std. N Mean P value Rate Deviation
>60 51 40.04 11.12
SERUM 41-60 32 55.69 10.75 AMYLASE <0.0001 (DAY 2) <40 17 79.18 11.58
Total 100 51.70 18.03
100.00
90.00 79.18 80.00
70.00
60.00 55.69
50.00 40.04 40.00
30.00
20.00
10.00
0.00 >60 41-60 <40
On day 2 serum amylase values are reduced in normal heart rate patients have 40.04 and 79.18 IU/L in those with severe bradycardia.
83
Respiratory Std. N Mean P value rate Deviation
<20/min 68 155.47 50.64
SERUM >20/min 1 278.00 - AMYLASE >20/min with <0.0001 31 407.94 94.65 (DAY1) cyanosis
Total 100 234.96 134.83
600.00
500.00
407.94 400.00
300.00 278.00
200.00 155.47
100.00
0.00 <20/min >20/min >20/min with cyanosis
Patients with impending respiratory failure have increased serum amylase values on day 1 shows 470.94IU/L compared to have normal RR patients mean amylase is 155.47
84 Std. Respiratory rate N Mean P value Deviation
<20/min 68 41.94 10.31
>20/min 1 72.00 - SERUM AMYLASE <0.0001 (DAY 2) >20/min with 31 72.45 12.68 cyanosis
Total 100 51.70 18.03
90.00
80.00 72.00 72.45 70.00
60.00
50.00 41.94 40.00
30.00
20.00
10.00
0.00 <20/min >20/min >20/min with cyanosis
85
SERUM Conscious and 58 158.07 81.81 AMYLASE rationale (DAY1) Impaired response to 30 295.53 105.55 verbal commands <0.0001 No reponse to verbal 12 455.17 74.00 commands
Total 100 234.96 134.83
600.00
500.00 455.17
400.00
295.53 300.00
200.00 158.07
100.00
0.00 Conscious and rationale Impaired response to verbal No reponse to verbal commands commands
Patients with normal sensorium have mean amylase on day 1 is 158.07
IU/L compared to patients with poor sensorium is 455.17 IU/L..
86
DEPRESSED Std. P value MENTAL STATUS N Mean Deviation
SERUM Conscious and 58 42.00 12.55 AMYLASE rationale (DAY 2) Impaired response to 30 59.67 14.79 verbal commands <0.0001 No reponse to verbal 12 78.67 8.41 commands
Total 100 51.70 18.03
100.00
90.00
78.67 80.00
70.00 59.67 60.00
50.00 42.00 40.00
30.00
20.00
10.00
0.00 Conscious and rationale Impaired response to verbal No reponse to verbal commands commands
On day 2 normal sensorium patients have 42 IU/L compared to 78.67
IU/L
87
Std. SEIZURES N Mean P value Deviation
SERUM AMYLASE Absent 92 214.83 119.06 <0.0001 (DAY1) Present 8 466.50 78.73
600.00
500.00 466.50
400.00
300.00
214.83 200.00
100.00
0.00 Absent Present
Day 1 serum amylase is significantly higher in who developed convulsions(466.50)
88
SEIZURES N Mean Std. Deviation P value
Absent 92 49.61 16.68 SERUM AMYLASE (DAY 2) 0.002 Present 8 75.75 16.26
100.00
90.00
80.00 75.75
70.00
60.00
49.61 50.00
40.00
30.00
20.00
10.00
0.00 Absent Present
On day 2 amyalse value in seizure pts is 75.75 IU/L;normal patients have 49.61
IU/L.
89
POP severity Std. N Mean P value score Deviation
SERUM AMYLASE Normal 39 115.54 18.13 (DAY1) Mild 29 209.17 21.98
Moderate 15 306.13 27.02 <0.0001
Severe 17 490.12 17.91
Total 100 234.96 134.83
600.00
490.12 500.00
400.00
306.13 300.00
209.17 200.00
115.54 100.00
0.00 Normal Mild Moderate Severe
In our study patients with severe category have significantly increased amylase 490.12 IU/L compared to normal patients have mean amylase is 115.54
IU/L in day 1.
90
POP Std. severity N Mean P value Deviation score
SERUM Normal 39 35.85 7.14 AMYLASE (DAY 2) Mild 29 50.14 8.00
Moderate 15 64.93 8.68 <0.0001
Severe 17 79.06 11.66
Total 100 51.70 18.03
100.00
90.00 79.06 80.00
70.00 64.93
60.00 50.14 50.00
40.00 35.85
30.00
20.00
10.00
0.00 Normal Mild Moderate Severe
On day 2 amylase values in severe category patients is 79.06 IU/L compared to normal patients is 35.85 IU/L…
91 Correlations
SERUM SERUM AMYLASE AMYLASE (DAY1) (DAY 2)
Pearson .974** .871** Correlation POP SCORE Sig. (2-tailed) <0.0001 <0.0001
N 100 100
92 VENTILATOR SUPPORT Std. NEEDED N Mean Deviation P value
SERUM No AMYLASE 68 155.47 50.64 (DAY1) <0.0001 Yes 32 403.88 95.90
600.00
500.00
403.88 400.00
300.00
200.00 155.47
100.00
0.00 No Yes
Patients who require ventilator support have increased serum amylase values 403.88 IU/L compared to patients doesnot require support is 155.47 IU/L.
93 VENTILATOR SUPPORT Std. NEEDED N Mean Deviation P value
SERUM No 68 41.94 10.31 AMYLASE <0.0001 (DAY 2) Yes 32 72.44 12.47
90.00
80.00 72.44 70.00
60.00
50.00 41.94 40.00
30.00
20.00
10.00
0.00 No Yes
Day 2 serum amylase is in patients with ventilator support is 72.44IU/L compared to patients not needed ventilator support is 41.94 IU/L….
94
Group Statistics
Std. OUTCOME N Mean P value Deviation
SERUM Alive 83 182.70 74.98 AMYLASE <0.0001 (DAY1) Dead 17 490.12 17.91
600.00
490.12 500.00
400.00
300.00
200.00 182.70
100.00
0.00 Alive Dead
Of patients with increased serum amylase value outcome of the patient is dead compared to alive patients.
95
Std. OUTCOME N Mean P value Deviation
SERUM Alive 83 46.10 13.38 AMYLASE <0.0001 (DAY 2) Dead 17 79.06 11.66
100.00
90.00 79.06 80.00
70.00
60.00
50.00 46.10
40.00
30.00
20.00
10.00
0.00 Alive Dead
96 DISCUSSION:
Organophosphorus poisoning is one of the most consuming poison world wide.In developing countries like India due to lack of adequate facilities first to categorize the patients those who will land up in respiratory failure, so we need some prognostic markers to predict the respiratory failure. of these serum amylase is one of the easiest low cost, available investigation .So the study undertaken was to assess prognostic significance and clinical outcome in organo phosphorus poisoning
In our study majority of patients were belong to age group between 31- 40 years ( 36%) followed by age group between 21-30 years(27%).
Majority of patients in the study group were males (69%) compared to females (31%). similiar male was more predominant in study observed by Goel et al, Kavya et al and Rajeev et al .
The compound most commonly consumed in our study group is
Monocrotophos(22%), followed by phorate (17%).. study done by subash et al most commonly compound consumption is malathion ,because due to availability of compounds have variation in regional distribution of land agriculture and economy of the patients.
Out of 100 patients taken in our study 68% patients does not need any ventilator support, compared to those who need 32%.And outcome is 83% are alive patients.
97 Clinical parameters were taken into our study was based on POP scale.
Pupillary size changes 50% patients showed more than 2mm size, followed by less than 2mm and pinpoint (16%).serum amylase on day 1 of size more than 2 mm mean value is 137.64 compared to pinpoint it is 460..By treatment amylase values are reduced from day 1 to day 2.Of those are >2mm on day 2 is mean amylase value is 38.72 compared to pinpoint is 75.25.
In our study group 63% patients does not develop fasciculation followed by 25% are developed either generalized or continuous but 12% patients develop both. .serum amylase of those does not develop in day 1 is 154.83 compared to those who have both is 486.67. on Day 2 patients with no fasciculation is 41.21 compared to both is 74.83..
Patients taken into our study 51% patients does not develop bradycardia,17% patients were show heart rate is less than 40.serum amylase on day 1 of normal heart rate patients is 141.45 compared to those who severe bradycardia is 483.53...on Day 2 serum amylase in normal patients is 40.04 compared to those who severe bradycardia is 79.18.
In our study patients with normal sensorium is 58% compared to those who not respond to oral commands is 12%. Mean serum amylase on day 1 in normal sensorium patients is 158.07 compared to poor sensorium patients is
455.17..on day 2 normal sensorium patients have value 42 compared to poor sensorium patients is 78.67..
98 Another manifestation taken account into our study is seizures. Patients not presented with seizures are 92 on day 1 amylase value is 214.83 compared to those have is 466.50.on Day 2 convulsions absent patients value is 49.61 compared to present patients is 75.75.
Based on POP scale patients with normal score in our study is 39,mild category(29),moderate category(15);severe (17)..serum amylase on day 1 of normal score is 115.54 compared to severe is 490.12..on day 2 amylase is 35.85 in normal patients compared to severe is 79.06…
One of the most important parameter is respiratory failure. .patients with normal RR is 68 compared to those developed tachypneic is 32 patients .day 1 serum amylase of normal RR is 155.47 compared to tachypneic is 407.94..On day 2 normal RR have amylase value is 41.94 compared to Tachypneic is 72.45. one of the study in japan conducted by sumiya et al increase in amylase value above the normal patients will develop respiratory failure.In our study 68 patients does not require ventilator support,32 patients needed ventilator support.. serum amylase on day 1 of normal patients is 155.47 compared to ventilator needed patients is 403.88.on day 2 normal patients mean serum amylase value is 41.94 compared to ventilator needed patients is 72.44..similiar to our study L in CL et al., found that increased serum amylase value predict ventilator support.Outcome of patients in our study group 83 patients were alive compared to dead patients is
17.mean amylase on day 1 of alive patients is 182.70 compared to dead is
490.12. on day 2 amylase value in alive patients is 46.10 compared to dead patients is 79.06
99 CONCLUSION:
1. From the observation of our study serum amylase is increased
significantly in organo phosphorus poisoning.
2. Increased serum amylase is significantly correlated with clinical
outcome of the patients.
3. Increased amylase is significantly associated with predicting
respiratory failure in organophosphorus patients.
4. Previously serum cholinesterase is used to assess the severity but one
of the cheapest available investigation is serum amylase is considered
as better indicator to assess severity in organophosphorus poisoning.
5. So, from the increased amylase values we can identify those who are
all risk for developing complications.
100 SUMMARY:
The study was conducted in our hospital with sample size of 100 patients during the period of from February 2018 to November 2019 those who are admitted with organophosphorus poisoning. Most common age group is affected in our study is between 31-40 years of age .Male patients were predominantly present in our study.
Most common compound consumed in our study is monocrotophos. serum amylase is increased significantly those who are presented with clinical features of pinpoint pupil, fasciculation, Altered mental status, bradycardia, seizures, respiratory failure. serum amylase day 1 and day 2 and other routine investigation are measured.
All the collected data were analysed statistically using appropriate statistical tests and P value is <0.0001 is considered significant. out of 100 patients 32 patients require ventilator support coincide significantly with increased amylase values on day 1,followed by treatment there is gradual reduction in the serum amylase on day 2.
In our study clinical outcome out of 100 patients, 17 were dead also have statistically significant in increase in serum amylase levels on first day.
From the observation of study it is concluded that increased serum amylase is considered as marker and it can predict the risk of those who developing complications like respiratory failure in organo phosphorus poisoning
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107 CONSENT FORM
STUDY TITLE:
“ A CLINICAL STUDY OF SERUM AMYALSE IN ORGANOPHOSPHORUS POISONING IN A TERTIARY CARE HOSPITAL”
DEPARTEMENT OF GENERAL MEDICINE GMKMCH -SALEM
PARTICIPANT NAME:
AGE:
SEX:
I.P. NO:
I confirm that I have understood the purpose of the above study. I have the opportunity to ask the question and all my questions and doubts have been answered to my satisfaction. I have been explained about the possible complications that may occur during and after medical procedure. I understand that my participation in the study is voluntary and that I am free to withdraw at any time without giving any reason. I understand that investigator, regulatory authorities and the ethics committee will not need my permission to look at my health records both in respect to the current study and any further research that may be conducted in relation to it, even if I withdraw from the study. I understand that my identity will not be revealed in any information released to third parties or published, unless as required under the law. I agree not to restrict the use of any data or results that arise from the study. I hereby consent to participate in this study. Time: Patient name;
Date: Signature / Thumb Impression of Patient: Place
Name and signature of the Investigator
108
ஆராய்ச் ஒப்�த ப�வம
ெபயர: ேததி: வய�: உள்ேநாயாள எண: பாலினம: ஆய் ேசர்க் எண:
இந் ஆய்வ� ேநாக்க மற்� வ�வரங்க ��ைமயாக எனக் ெதள�வாக வ�ளக்கப்பட .இவ்வாய்வ இ�ந் நான எந் ேநர�ம ப�ன்வாங்கல என்பைத� அதனால எனக் எந் பாதிப்� இல்ை என்பைத� ெதள�வாக ��ந் ெகாண்ேட. ���கைள அல்ல க�த்�கை ெவள�ய��ம ேபாேதா அல்ல ஆய்வ� ேபாேதா என்�ைட ெபயைரேயா அல்ல அைடயாளங்கைளேய ெவள�ய�ட மாட்டார் என்பைத� அறிந் ெகாண்ேட. இந் ஆய்வ� எவ்வ� நிர்பந்த இன்ற என� ெசாந் வ��ப்பத்த ேப�ல நான பங் ெப�கின்ேற. நான �யநிைன�ட�ம �� �தந்திரத்�ட இந் ம�த்� ஆராய்ச்சிய ேசர்த்�க்ெக சம்மதிக்கின்.
ஆராய்சியாள ஒப்ப பங்ேகற்பா ஒப்ப (அ) இட� ெப�வ�ரல்ேரை
109 PROFORMA:
Name :
Age
Sex:
Address:
Ip no:
Occupation:
Date of admission:
Date of discharged/ Date of expired:
Compound identified:
Clinical history: clinical history details elaboration of presenting complaints ,past history of any co morbidities, drug history, treatment history, personal history,
Clinical examination:
Vitals:PR;BP;RR;SPO2
General examination and other systemic examination :
110 POP SCORE:
S.NO PARAMETER SCORE
1. MIOSIS:
Pupil >2mm 0
Pupil<2 mm 1
Pinpoint 2
2. FASCICULATIONS
None 0
Present but not generalized or continuous 1
Generalized and continuous 2
3 RESPIRATORY RATE
RR <20/minute 0
RR>20/minute 1
RR >20/minute with central cyanosis 2
4 PULSE RATE
Pulse rate>60 0
Pulse rate 40-60 1
Pulse rate <40 2
111 S.NO PARAMETER SCORE
5 LEVEL OF CONSCIOUSNESS
Conscious and rationale 0
Impaired, responds to oral commands 1
Impaired, no response to oral commands 2
6. SEIZURES
Absent 0
Present 1
TOTAL
Laboratory investigation:
Complete blood count:
Renal function test:
Liver function test:
Chest x ray and E cg
Us g abdomen &pelvis:
Serum amylase (DAY 1 & DAY 2):
Treatment:
Whether patient requires ventilator support or not:
Outcome :Alive or dead
112 MASTER CHART
SEX SNO (DAY1) SERUM MENTAL FAILURE SEIZURES SEVERITY OUTCOME OUTCOME (PRESENT) (PRESENT) (PRESENT) POP SCORE POP SCORE DEPRESSED COMPOUND HEART RATE AGE (YEARS)AGE VENTILATOR ( YES OR NO ) YES ( OCCUPATION (ALIVE/DEAD) RESPIRATORY RESPIRATORY FASICULATION FASICULATION (BRADYCARDIA AMYLASE(DAY 2) SERUM AMYLASE MIOSIS (PRESENT) STATUS(PRESENT) SUPPORT NEEDED SUPPORT
1 26 M COOLIE DIMETHOATE 1 1 0 0 0 0 2 MILD 222 54 NO ALIVE 2 32 F FARMER MONOCROTOPHOS 2 2 2 2 0 1 9 SEVERE 504 62 YES DEAD 3 59 M FARMER PHORATE 1 1 1 0 0 0 3 MILD 202 50 NO ALIVE 4 27 M STUDENT PHORATE 1 1 1 1 1 0 5 MOD 278 72 YES ALIVE 5 22 F HOUSEWIFE DIMETHOATE 1 0 1 0 0 0 2 MILD 190 44 NO ALIVE 6 18 M COOLIE DICHLORIVAS 0 0 0 0 0 0 0 NORMAL 142 34 NO ALIVE 7 38 M FARMER MONOCROTOPHOS 2 2 2 2 1 1 10 SEVERE 444 56 YES DEAD 8 21 F HOUSEWIFE DIAZINON 0 0 0 0 0 0 0 NORMAL 100 32 NO ALIVE 9 36 M COOLIE DIMETHOATE 1 0 0 0 0 0 1 MILD 194 40 NO ALIVE 10 30 M COOLIE MONOCROTOPHOS 2 2 2 2 2 0 10 SEVERE 476 74 YES DEAD 11 26 F COOLIE PHORATE 1 1 0 0 1 0 3 MILD 206 46 NO ALIVE 12 29 M FARMER DICHLORIVAS 1 0 1 0 1 0 3 MILD 246 52 NO ALIVE 13 20 M STUDENT ENDOSULFAN 0 0 0 0 0 0 0 NORMAL 142 32 NO ALIVE 14 31 M COOLIE DIMETHOATE 1 0 1 0 1 0 3 MILD 210 44 NO ALIVE 15 58 F OTHERS FOLIDOL 0 0 0 0 0 0 0 NORMAL 102 30 NO ALIVE 16 56 M COOLIE PHORATE 1 1 1 2 1 0 6 MOD 288 66 YES ALIVE 17 39 M FARMER PHORATE 1 1 0 0 0 0 2 MILD 222 58 NO ALIVE 18 38 M COOLIE MALATHION 0 0 0 0 0 0 0 NORMAL 112 28 NO ALIVE 19 58 F FARMER PHORATE 1 1 1 2 1 0 6 MOD 300 76 YES ALIVE 20 26 M FARMER MALATHION 0 0 0 0 0 0 0 NORMAL 130 42 NO ALIVE 21 44 F HOUSEWIFE MALATHION 0 0 0 0 0 0 0 NORMAL 120 38 NO ALIVE 22 42 M COOLIE DICHLORIVAS 1 0 0 0 1 0 2 MILD 238 50 NO ALIVE 23 30 M STUDENT PHORATE 2 1 0 2 2 0 7 MOD 320 68 YES ALIVE 24 42 M COOLIE MALATHION 0 0 0 0 0 0 0 NORMAL 110 36 NO ALIVE 25 29 F HOUSEWIFE PHORATE 1 1 0 0 1 0 3 MILD 236 48 NO ALIVE
113
SEX SNO (DAY1) SERUM MENTAL FAILURE SEIZURES SEVERITY OUTCOME OUTCOME (PRESENT) (PRESENT) (PRESENT) POP SCORE POP SCORE DEPRESSED COMPOUND HEART RATE AGE (YEARS)AGE VENTILATOR ( YES OR NO ) YES ( OCCUPATION (ALIVE/DEAD) RESPIRATORY RESPIRATORY FASICULATION FASICULATION (BRADYCARDIA AMYLASE(DAY 2) SERUM AMYLASE MIOSIS (PRESENT) STATUS(PRESENT) SUPPORT NEEDED SUPPORT
26 28 M STUDENT DIAZINON 0 0 0 0 0 0 0 NORMAL 98 34 NO ALIVE 27 23 M FARMER DICHLORIVAS 0 0 0 0 0 0 0 NORMAL 90 30 NO ALIVE 28 33 F HOUSEWIFE MONOCROTOPHOS 1 1 2 2 2 1 9 SEVERE 506 92 YES DEAD 29 30 M STUDENT TRIAZOPHOS 0 0 0 0 0 0 0 NORMAL 122 36 NO ALIVE 30 62 M COOLIE DIMETHOATE 1 1 1 0 0 0 3 MILD 240 68 NO ALIVE 31 33 M FARMER MALATHION 0 0 0 0 0 0 0 NORMAL 140 48 NO ALIVE 32 17 M COOLIE PHORATE 1 1 1 2 0 0 5 MOD 280 82 YES ALIVE 33 33 M STUDENT FOLIDOL 0 0 0 0 0 0 0 NORMAL 144 48 NO ALIVE 34 56 M FARMER MONOCROTOPHOS 1 1 2 2 2 0 8 SEVERE 490 84 YES DEAD 35 32 F COOLIE DIMETHOATE 0 0 1 0 1 0 2 MILD 200 50 NO ALIVE 36 32 M STUDENT DICHLORIVAS 0 0 0 0 0 0 0 NORMAL 88 30 NO ALIVE 37 34 M COOLIE PHORATE 1 0 1 2 1 0 5 MOD 280 60 YES ALIVE 38 30 M COOLIE MALATHION 0 0 0 0 0 0 0 NORMAL 84 32 NO ALIVE 39 27 M OTHERS DIAZINON 0 0 0 0 0 0 0 NORMAL 112 56 NO ALIVE 40 32 M COOLIE MONOCROTOPHOS 2 2 2 2 1 0 9 SEVERE 488 82 YES DEAD 41 43 F COOLIE DICHLORIVAS 1 0 1 0 1 0 3 MILD 238 52 NO ALIVE 42 40 M COOLIE TRIAZOPHOS 0 0 0 0 0 0 0 NORMAL 136 34 NO ALIVE 43 59 M FARMER MONOCROTOPHOS 1 1 1 2 0 0 5 MOD 290 56 YES ALIVE 44 42 M COOLIE PHORATE 0 0 1 0 1 0 2 MILD 232 48 NO ALIVE 45 21 M STUDENT MALATHION 0 0 0 0 0 0 0 NORMAL 120 34 NO ALIVE 46 74 F HOUSEWIFE MONOCROTOPHOS 1 2 2 2 2 1 10 SEVERE 478 76 YES DEAD 47 33 M OTHERS FOLIDOL 0 0 0 0 0 0 0 NORMAL 100 28 NO ALIVE 48 32 M FARMER DIMETHOATE 1 0 0 0 0 0 1 MILD 176 54 NO ALIVE 49 62 F HOUSEWIFE PHORATE 2 1 0 2 1 0 6 MOD 340 70 YES ALIVE 50 28 F HOUSEWIFE MALATHION 0 0 0 0 0 0 0 NORMAL 110 38 NO ALIVE 51 38 M COOLIE MONOCROTOPHOS 2 1 2 2 1 1 9 SEVERE 498 96 YES DEAD 52 43 F HOUSEWIFE DICHLORIVAS 0 0 0 0 0 0 0 NORMAL 128 30 NO ALIVE 53 34 M FARMER DIMETHOATE 1 0 0 0 0 0 1 MILD 180 56 NO ALIVE
114
SEX SNO (DAY1) SERUM MENTAL FAILURE SEIZURES SEVERITY OUTCOME OUTCOME (PRESENT) (PRESENT) (PRESENT) POP SCORE POP SCORE DEPRESSED COMPOUND HEART RATE AGE (YEARS)AGE VENTILATOR ( YES OR NO ) YES ( OCCUPATION (ALIVE/DEAD) RESPIRATORY RESPIRATORY FASICULATION FASICULATION (BRADYCARDIA AMYLASE(DAY 2) SERUM AMYLASE MIOSIS (PRESENT) STATUS(PRESENT) SUPPORT NEEDED SUPPORT
54 40 F HOUSEWIFE MONOCROTOPHOS 2 1 2 2 1 0 8 SEVERE 510 98 YES DEAD 55 34 M COOLIE DIAZINON 0 0 0 0 0 0 0 NORMAL 132 42 NO ALIVE 56 33 F COOLIE PHORATE 1 0 0 0 0 0 1 MILD 198 66 NO ALIVE 57 21 M FARMER DIMETHOATE 1 1 1 0 0 0 3 MILD 246 58 NO ALIVE 58 39 M COOLIE MONOCROTOPHOS 1 1 1 2 1 0 6 MOD 300 62 YES ALIVE 59 44 M COOLIE DIMETHOATE 0 0 1 0 0 0 1 MILD 194 42 NO ALIVE 60 57 M FARMER MONOCROTOPHOS 2 2 2 2 2 0 10 SEVERE 490 88 YES DEAD 61 27 F COOLIE DIMETHOATE 0 0 0 0 0 0 0 NORMAL 96 30 NO ALIVE 62 38 M OTHERS DICHLORIVAS 1 0 1 0 0 0 2 MILD 212 42 NO ALIVE 63 37 M COOLIE MONOCROTOPHOS 2 2 2 2 2 1 11 SEVERE 506 78 YES DEAD 64 19 M FARMER FOLIDOL 0 0 0 0 0 0 0 NORMAL 100 30 NO ALIVE 65 30 F COOLIE DICHLORIVAS 0 0 0 0 0 0 0 NORMAL 112 38 NO ALIVE 66 33 M STUDENT DIMETHOATE 0 0 1 0 1 0 2 MILD 208 50 NO ALIVE 67 28 M COOLIE DIMETHOATE 0 1 1 0 1 0 3 MILD 230 56 NO ALIVE 68 58 M FARMER MONOCROTOPHOS 2 1 2 2 1 0 8 SEVERE 488 76 YES DEAD 69 33 F HOUSEWIFE MALATHION 0 0 0 0 0 0 0 NORMAL 102 34 NO ALIVE 70 23 M COOLIE DICHLORIVAS 0 0 1 0 0 0 1 MILD 180 44 NO ALIVE 71 42 M COOLIE PHORATE 0 1 1 2 2 0 6 MOD 320 66 YES ALIVE 72 40 F COOLIE DICHLORIVAS 0 0 1 0 1 0 2 MILD 202 42 NO ALIVE 73 44 M OTHERS FOLIDOL 0 0 0 0 0 0 0 NORMAL 138 48 NO ALIVE 74 31 M COOLIE PHORATE 1 0 1 0 1 0 3 MILD 178 66 NO ALIVE 75 18 F STUDENT MALATHION 0 0 0 0 0 0 0 NORMAL 88 28 NO ALIVE 76 30 F COOLIE MONOCROTOPHOS 1 1 1 2 0 0 5 MOD 290 62 YES ALIVE 77 38 M COOLIE TRIAZOPHOS 0 0 0 0 0 0 0 NORMAL 100 30 NO ALIVE 78 43 M COOLIE MONOCROTOPHOS 2 2 1 2 1 0 8 SEVERE 478 70 YES DEAD 79 31 F HOUSEWIFE DIMETHOATE 0 0 0 0 0 0 0 NORMAL 130 34 NO ALIVE 80 72 M FARMER MONOCROTOPHOS 2 2 2 2 2 1 11 SEVERE 516 90 YES DEAD 81 46 M COOLIE MONOCROTOPHOS 1 2 2 2 2 0 9 SEVERE 498 76 YES DEAD
115
SEX SNO (DAY1) SERUM MENTAL FAILURE SEIZURES SEVERITY OUTCOME OUTCOME (PRESENT) (PRESENT) (PRESENT) POP SCORE POP SCORE DEPRESSED COMPOUND HEART RATE AGE (YEARS)AGE VENTILATOR ( YES OR NO ) YES ( OCCUPATION (ALIVE/DEAD) RESPIRATORY RESPIRATORY FASICULATION FASICULATION (BRADYCARDIA AMYLASE(DAY 2) SERUM AMYLASE MIOSIS (PRESENT) STATUS(PRESENT) SUPPORT NEEDED SUPPORT
82 34 F COOLIE FOLIDOL 0 0 0 0 0 0 0 NORMAL 110 32 NO ALIVE 83 20 M FARMER DIMETHOATE 0 0 1 0 1 0 2 MILD 200 46 NO ALIVE 84 29 M COOLIE MALATHION 0 0 0 0 0 0 0 NORMAL 134 32 NO ALIVE 85 56 F HOUSEWIFE MONOCROTOPHOS 2 2 2 2 2 0 10 SEVERE 496 80 YES DEAD 86 62 M COOLIE PHORATE 1 0 2 2 2 0 7 MOD 366 72 YES ALIVE 87 41 M FARMER MALATHION 0 0 0 0 0 0 0 NORMAL 126 42 NO ALIVE 88 38 F HOUSEWIFE DICHLORIVAS 0 0 0 0 0 0 0 NORMAL 148 30 NO ALIVE 89 64 M COOLIE MONOCROTOPHOS 2 0 1 2 1 0 6 MOD 340 50 YES ALIVE 90 31 M COOLIE DIAZINON 0 0 0 0 0 0 0 NORMAL 102 34 NO ALIVE 91 18 M STUDENT MONOCROTOPHOS 2 2 2 2 0 0 8 SEVERE 466 66 YES DEAD 92 36 F STUDENT TRIAZOPHOS 0 0 0 0 0 0 0 NORMAL 118 54 NO ALIVE 93 33 M COOLIE FOLIDOL 0 0 0 0 0 0 0 NORMAL 134 42 NO ALIVE 94 37 F COOLIE PHORATE 1 1 1 2 1 1 7 MOD 280 56 YES ALIVE 95 17 M STUDENT DIMETHOATE 0 0 1 0 1 0 2 MILD 210 48 NO ALIVE 96 23 F STUDENT FOLIDOL 0 0 0 0 0 0 0 NORMAL 112 38 NO ALIVE 97 66 M COOLIE MONOCROTOPHOS 1 1 1 2 1 0 6 MOD 320 56 YES ALIVE 98 30 M STUDENT MONOCROTOPHOS 1 0 0 0 0 0 1 MILD 176 34 NO ALIVE 99 57 F COOLIE DICHLORIVAS 0 0 1 0 1 0 2 MILD 200 46 NO ALIVE 100 22 M STUDENT DIMETHOATE 0 0 0 0 0 0 0 NORMAL 94 30 NO ALIVE
116