PREDICTION OF VENTILATORY SUPPORT IN PATIENTS WITH ORGANOPHOSPHORUS POISONING

By

DR.UDAYASHANKAR R.HIREGOUDAR

Dissertation Submitted to the

Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka,

In partial fulfilmentof the requirements for the degree of

DOCTOR OF MEDICINE

IN

GENERAL MEDICINE

Under the guidance of

DR.VIJAY M. BENGLORKAR

PROFESSOR, DEPARTMENT OF GENERAL MEDICINE

DEPARTMENT OF GENERAL MEDICINE

RAJARAJESWARI MEDICAL COLLEGE AND HOSPITAL, BANGALORE-560074

2011-2014

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA

DECLARATION BY THE CANDIDATE

I hereby declare that this Dissertation entitled“PREDICTION OF VENTILATORYSUPPORT IN PATIENTS WITH ORGANOPHOSPHORUS POISONING”is a bonafide and a genuine research work carried out by me under the guidance ofDr.VIJAY M. BENGLORKAR,Professor, Department ofGENERAL MEDICINE,Rajarajeswari Medical College and Hospital, Bangalore.The dissertation has not formed the basis for the award of any degree to me previously by any other University.

Dr.Udayashankar R.Hiregoudar

Post Graduate student, Dept.of General Medicine

Date: Rajarajeswari Medical College and Hospital,

Place: Bangalore

CERTIFICATE BY THE GUIDE

This is to certify that the dissertation entitled “PREDICTION OF VENTILATORY SUPPORT IN PATIENTS WITH ORGANOPHOSPHORUS POISONING”is a bonafide research work done byDr.UDAYASHANKAR R. HIREGOUDAR, Post Graduate student, in Department of GENERAL MEDICINE, RajarajeswariMedical College and Hospital, Bangalore. It was done under my guidance in partial fulfilment of the requirement for the M.D.,in General Medicine degree examination of Rajiv Gandhi University of health Science to be held in 2014.

Dr. Vijay M. Benglorkar

Professor, Dept. of General Medicine

Date: Rajarajeswari Medical College and Hospital

Place: Bangalore

CERTIFICATE BY THE CO-GUIDE

This is to certify that the dissertation entitled “PREDICTION OF VENTILATORY SUPPORT IN PATIENTS WITH ORGANOPHOSPHORUS POISONING” is a bonafide research work done by Dr. UDAYASHANKAR R. HIREGOUDAR, Post Graduate student, in Department of GENERAL MEDICINE, Rajarajeswari Medical College and Hospital, Bangalore. It was done under my co-guidance in partial fulfilment of the requirement for the M.D., in General Medicine degree examination of Rajiv Gandhi University of health Science to be held in 2014.

Dr. Rangalakshmi. S

Professor, Dept. of Anaesthesiology

Date: Rajarajeswari Medical College and Hospital

Place: Bangalore

ENDORSEMENT BY THE HEAD OF DEPARTMENT

This is to certify that the dissertation entitled “PREDICTION OF VENTILATORY SUPPORT IN PATIENTS WITH ORGANOPHOSPHORUS POISONING” is a bonafide research work done byDr.UDAYASHANKAR R. HIREGOUDAR, Post Graduate Student, in Department of GENERAL MEDICINE, Rajarajeswari Medical College and Hospital,Bangalore, under the guidance and supervision of Dr. VIJAY M. BENGLORKAR, Professor,Department of GENERAL MEDICINE, Rajarajeswari Medical College and Hospital, Bangalore, in partial fulfilment of the regulations for the M.D., in GENERAL MEDICINE degree examination of Rajiv Gandhi University of Health Sciences to be held in 2014.

Dr.Krishna M.V.

Professor Head of the Dept.

Department of General Medicine Date: Rajarajeswari Medical College and Hospital,

Place: Bangalore

ENDORSEMENT BY THE HEAD OF THE INSTITUTION

This is to certify that the dissertation entitled “PREDICTION OF VENTILATORY SUPPORT IN PATIENTS WITH ORGANOPHOSPHORUS POISONING” is a bonafide research work done by Dr. UDAYASHANKAR R. HIREGOUDAR, Post Graduate Student, in Department of GENERAL MEDICINE, Rajarajeswari Medical College and Hospital, Bangalore, under the guidance and supervision of Dr.VIJAY M. BENGLORKAR, Professor, Department of GENERAL MEDICINE, Rajarajeswari Medical College and Hospital, Bangalore, in partial fulfilment of the regulations for the M.D., in GENERAL MEDICINE degree examination of Rajiv Gandhi University of Health Sciences to be held in 2014.

Dr. H.Rangappa

Dean

Date: Rajarajeswari Medical College and Hospital,

Place: Bangalore

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA, BANGALORE.

COPY RIGHT

DECLARATION BY THE CANDIDATE

I hereby declare that the Rajiv Gandhi University of Health Sciences, Karnataka shall have the rights to preserve, use and disseminate this dissertation in print or electronic format for academic/research purpose.

Dr.Udayashankar R. Hiregoudar

Post Graduate student, Dept. of General Medicine

Date: Rajarajeswari Medical College and Hospital

Place: Bangalore

© Rajiv Gandhi University of Health Sciences, Karnataka.

ACKNOWLEDGMENT

I thank Almighty for having blessed me with the ability to accomplish this task. I take this opportunity to express my heartfelt gratitude to my beloved family members for the dreams they have dreamt and hardships they have gone through to make me stand where I am today.

I consider myself fortunate to have Dr. Vijay M. Benglorkar, Professor, Department ofGeneral Medicine as my guide and mentor. I express my thanks with heartfelt appreciation for his valuable guidance, optimistic attitude, professional insight and meticulous support which helped me to be a more organised person andaccomplish my goal in my carrier.

My special thanks to Dr. Rangalaxmi, Professor, Dept. of Anaesthesiology who helped me as a co-guide with her valuable advices in critical situations during the ICU care of our patients throughout my research work.

Icannot find words to express my heartfelt gratitude and respect to Dr. Krishna M.V, Professor and HOD, Department of General Medicine,a person with humbleness and great sincerity, whose high inspiration, timely help and professional guidance made my carrier more easier and to achieve the tasks in the profession.

It is worth mentioning names of my senior professors, Dr. Rangamani (Professor emeritus), Dr.Chikkananjaiah, Dr. Mamatha Patil and Dr. Ajithkumar without whom it would have been a difficult curriculum. They walked me throughout my post Graduate carrier with their professional guidance, skilful teaching and priceless timely advices with a sense of care which made me to sail through the hardship of carrier. I sincerely thank them with deep sense of respect.

My heartfelt thanks to all the other teaching staff of our Medicine Department who left an indelible impression in my mind by their constant help and encouragement during my study.

I am grateful to my fellow post graduates and non teaching staff of my department for their help and support.

My sincere thanks to thestaff and Postgraduates of Dept. of Anaesthesia, Dept. of Chest and TB diseases, Dept. of Psychiatry, Laboratory staff, ICU and ward nursing staff for their complete cooperation and help during my study.

It is incomplete without thanking all my patients involved in the study who are the key to my thesis work and their relatives for their full cooperation. Finally I pay my respect to all those patients who lost their lives and also have been the source of my data collection.

Dr.Udayashankar R. Hiregoudar

Post Graduate student, Dept. of General Medicine

Date: Rajarajeswari Medical College and Hospital,

Place: Bangalore

ABBREVIATIONS

Ach -- Acetylchonine

Ache -- Acetylcholine esterase

BP – Blood pressure

CBC -- Complete blood count

CPK -- Creatinine phosphokinase

CVS– Cardiovascular system

CXR -- Chest X ray

Dicro– Dicrotophos

ECG– Electrocardiography

GCS – Glasgow coma scale

Hrs – Hours

IMS -- Intermediate syndrome

Mono – Monocrotophos

MS -- Musculoskeletal

N – Normal

OP -- Organophosphate

RBS – Random blood sugar

RR– Respiratory rate

RS– Respiratory system

ABSTRACT

Background and Objectives:

India is basically an agricultural country where pesticides and insecticides are abundantly used. Because of the widespread usage and an easier availability for the general population it natural to have these compounds to be misused for suicidal and some instances for homicidal purposes. In the recent years it has been increased to a threatening level and causing a major health challenge. As the major leading cause of death in organophosphate poisoning is respiratory failure, ventilator support for the hospital admitted patients has proven to be most beneficial in saving their lives.

Hence the present study was aimed to determine the pseudocholinesterase, random blood sugar and creatinine phosphokinase levels and to predict the need of ventilator support in these poisoning patients.

Methods:

50 patients of organophosphorus compound poisoning who met the inclusion and exclusion criteria were selected for this direct observational study. Patient’s history was taken as per the standard proforma. In case of seriously ill or sick patients, history was collected from the patients. Thorough clinical examination and all the necessary investigations were done. Body fluids were collected under aseptic precautions. All the laboratory reports were analysed with proper followup of patients and documentation was done for clinical events. Later the results were analysed using standard statistical methods.

Results:

The organophosphorus poisoning constituted 56% of total poisoning cases

admitted during the study period. The males constituted 58% of cases and females constituted 42% of cases. The vulnerable age group was between 18 to 25 years.

94% consumed with intention of suicide whereas 6% of cases were accidental and spraying category.Metacid was the common culprit. Vomiting and pain abdomen were common symptoms while miosis, tachycardia, altered sensorium were common signs.28% patients required assisted ventilation.64.29% patients were ventilated within first 24 hours..Among 14 patients (14.28%) who required assisted ventilator support, almost all had low levels of pseudocholinesterase levels (P < 0.001) and high levels of both random blood sugar (P < 0.004) and CPK levels (P < 0.003).

Patients who were on ventilator support had the longer duration of hospital stay than the patients who were not on ventilatory support. Out of 14 patients who vent on ventilatory support 2 died with 4% of overall mortality rate in the study.

Conclusion:

The patients in the study group who had decreased levels of pseudocholinesterase levels and increased random blood sugar and CPK levels were more prone for the requirement of assisted ventilation.Hence, in Organophosphosphate poisoning it can be predicted that the patients with low levels of Pseudo cholinesterase and high levels of random blood sugar and CPK may require ventilator support.

TABLE OF CONTENTS

Sl. No. / Chapters / Page No.
1 /

Introduction

/ 1
2 /

Aims and Objectives

/ 2
3 /

Review of literature

/ 3
4 /

Materials and methods

/ 54
5 /

Results

/ 56
6 /

Discussion

/ 87
7 /

Conclusion

/ 91
8 /

Summary

/ 93
9 /

Bibliography

/ 95
10 /

Annexure

/ 100

LIST OF TABLES

Sl. No. / Title / Page No.
1 / Commonly encountered organophosphates in hospital emergencies / 6
2 / Less commonly encountered organophosphates / 7
3 / Organophosphates with severity of toxicity / 8
4 / Symptoms and signs of cholinergic overactivity manifested in different organ systems / 18
5 / Differential diagnosis of organophosphate poisoning / 19
6 / Difference between intermediate syndrome & delayed
neuropathy / 26
7 / Grading of severity of organophosphorus poisoning / 36
8 / Bardin et al Grading in intensive care unit / 37
9 / Reviced grading(Bardin and Van Eeden) / 38
10 / Grading on the basis of severity of poisoning / 38
11 / Glasgow coma scale / 39
12 / Treatment of organophosphate poisoning / 48
13 / Supportive therapy / 49
14 / Treatment schedule / 50
15 / Modes of ventilation / 52
16 / Age distribution of the patients studied / 61
17 / Gender distribution of the patients studied / 62
18 / Occupation of the patient / 63
19 / Individual OP compound and need for ventilator support / 64
20 / Latency to ventilation / 65
21 / Effect of time lag to specific treatment / 66
22 / Predominant symptoms on admission / 67
23 / Examination / 68
24 / Treatment / 73
25 / No. of patients required ventilator support / 74
26 / Effect of sensorium on need of ventilator support / 75
27 / Requirement of ventilator support in relation to severity of poisoning / 76
28 / Nature of poisoning of the study group / 77
29 / Investigations / 78
30 / Summary of the study / 83
31 / Final outcome of the study / 85

LIST OF FIGURES

Sl. No / Title / Page No.
1 / Hydrolysis of acetyl choline by acetylcholinesterase
Reactivation of alkyl phosphorylated acetyl cholinesterase / 13
2 / ANS and effector organ manifestation of toxicity / 16
3 / Receptors at different levels / 17
4 / Age distribution / 61
5 / Gender distribution / 62
6 / Occupation of the patients / 63
7 / Individual compound and distribution / 64
8 / Latency to ventilation / 65
9 / Effect of time lag to specific treatment / 66
10 / Symptoms on admission / 67
11 / Pulse rate / 69
12 / Blood pressure / 69
13 / Patients with Glasgow coma scale / 70
14 / Fasciculations / 70
15 / Convulsions / 71
16 / Cardiovascular system / 71
17 / Respiratory system / 72
18 / Respiratory rate / 72
19 / Pupil size / 72
20 / Dosage of atropine / 73
21 / Patients on ventilator / 74
22 / Glasgow coma scale / 75
23 / Severity of poisoning / 76
24 / Severity of poisoning / 77
25 / Serum pseudocholinesterase levels / 79
26 / Complete blood count / 79
27 / Blood urea and Sr. creatinine levels / 80
28 / Random blood sugar levels / 80
29 / Electrocardiogram / 81
30 / Creatinine phosphokinase levels / 81
31 / Oxygen saturation / 82
32 / Chest X ray / 82
33 / Duration of stay in the hospital / 83
34 / Outcome / 84
35 / Nature of poisoning / 84
36 / Pseudocholinesterase levels and Ventilatory support / 85
37 / RBS levels and ventilatory support / 86
38 / CPK levels and ventilatory support / 86

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