RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA

BANGALORE.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. Name of the candidate and address

Dr. DENNY MAMMEN A.

POST GRADUATE IN GENERAL MEDICINE

S.NIJALINGAPPA MEDICAL COLLEGE AND H.S.K HOSPITAL & RESEARCH CENTRE, NAVANAGAR, BAGALKOT- 587102

2 Name of the institutionS.NIJALINGAPPA MEDICAL COLLEGE AND H.S.K HOSPITAL & RESEARCH CENTRE, NAVANAGAR, BAGALKOT- 587102

3 Course of study and subject M.D. IN GENERAL MEDICINE

4 Date of admission to the course 30TH JUNE 2014

5 Title of the topic“STUDY OF LEVEL OF SERUM CREATINE PHOSPHOKINASE AS PROGNOSTIC INDICATOR IN ACUTE ORGANOPHOSPHORUS POISONING.”

6. Brief resume of intended work:

6.1 Need for study:

Organophosphorus(OP)insecticides are arguably one of the commonest causes of

morbidity and mortality due to poisoning worldwide especially in developing

countries like India. The morbidity and mortality depends on the time lag between the

exposure and the onset of management. With increased use of compounds for

agricultural and industrial purposes and due to easy access and low cost, they are

becoming a major source of health hazard. So it is cardinal to recognize the entire

spectrum of symptoms. Identification, risk stratification, early diagnosis and prompt

treatment of OP poisoning victims are equally vital.

These compounds act by inhibiting the enzyme acetylcholinesterase which result in

accumulation of acetylcholine in nervous tissue and effector organs, principal site

being the peripheral nervous system.

Patients with acute Organophosphorus(OP) poisoning are usually monitored by using

serum acetylcholinesterase level which are expected to fall. It is not specific and does

not correlate with the severity of poisoning and cannot be used as a prognostic

indicator. Estimation of Creatine Kinase is easy and levels are increased both in acute

phase as well as in intermediate syndrome due to muscle fibre necrosis.

Considering these factors this study is being undertaken.

6.2.Review of Literature:

Kuntal Bhattacharyya et al conducted a prospective study in 2011 in Department of Medicine,Calcutta Medical College in which they studied 63 patients of OP poisoning to find out the level of creatine kinase and its prognostic significance.

The CPK level was estimated for 61 patients. Two patients (Initial CPK 1138 IU/L & 1086 IU/L) died out of complications during the course of therapy on day 3 & day 5 respectively.It was found that mortality was more in patients with high initial CPK level. Another 3 patients developed intermediate syndrome on day 3,had initial CPK level 1138 IU/L & concluded serum CPK can be an efficient

biomarker in case of acute OP poisoning.

S.B. Agarwal, V.K. Bhatnagar, et al in the year 2007 conducted a prospective study in acute organophosphate poisoning patients admitted to Outdoor Patient Department of B.J. Medical College and Civil Hospital, Ahmedabad – 380016, India .121 patients were studied and found that the levels of serum LDH and CK were significantly elevated (p≤0.01) in poisoning cases indicating muscular functional impairment due to OP toxicity.

The CK activity was significantly increased in poisoning cases (p≤0.01) and comparatively marked elevation was observed among the expired patients.

Dilshad A Khan, Mahwish M Bhatti, Farooq A Khan, Syed T Naqvi, Karam A, Department of Pathology, Army Medical College, in 2008, conducted a prospective study on 109 patients and concluded that butryl cholinesterase activity was significantly decreased in the pesticides exposed farmers as compared to controls (P<0.001).

Plasma biochemical markers including ALT, AST, CK, LDH and phosphate were significantly raised in the pesticides exposed farmers as compared to control group (P<0.001). Total pesticides residues revealed a significant positive correlation with AST , LDH, ALT.

Rajdip sen, Nayak J, Khadanga S did a single centered cross sectional study over a period of one year on 100 patients of OP poisoning and concluded that Serum Creatinine Phosphokinase shows a strong degree of positive correlation with the severity of poisoning and can be used as a predictor of outcome in organophosphorus poisoning.

If the Serum CPK value remains persistently above 900 IU /L throughout the course of the disease, it is associated with higher rate of complications and mortality.

Nermeen A, M Hassan, Abdelmonem G. Madboly, Derpartment of Forensic medicine in Benha university hospital, Egypt conducted a prospective clinical study on 60 patients of OP poisoning during the period from 1st October 2012 to 31st March 2013 and found that Serum CPK level can be used as an alternative biomarker in diagnosis or stratifying severity of acute OP poisoning, as it is cheap, easily available, especially in developing countries and Serial measurements of serum CPK levels in acute OP poisoning can predict the prognosis.

6.3.Objective of study:1. Clinical assessment and categorization of organophosphorus poisoning cases

on admission based on Peradeniya Organophosphorus Poisoning scale.

2. To estimate the serum levels of creatine phosphokinase in acute organophosphorus poisoning and to correlate the same with clinical severity scoring at admission and serially till discharge.

7.MATERIALS AND METHODS

7.1. Source of data:

This consists of patients admitted in Department of General Medicine at S.Nijalingappa Medical College & HSK Hospital and Research Centre, Navanagar, Bagalkot.

7.2. Method of collection of data:

A. Study design: Cross sectional prospective study.

B. Study period:

C. Place of study:

The study is planned to be conducted in S.Nijalingappa Medical College & HSK Hospital and Research Centre, Navanagar, Bagalkot.

D. Sample size:

E. Inclusion criteria:

All cases of acute organophosphorus poisoning admitted to our hospital within 12 hours of consumption of the poison irrespective of age and sex whose caregivers are willing to give written informed consent.

F. Exclusion criteria:

1. Other non organophosphate poisoning.

2. Consumption of poison with alcohol.

3. Known medical illness like chronic liver disease, myopathy, malignancy, renal failure, autoimmune disorder, coronary artery disease.

4. Patients on chronic drugs like statins, fibrates, steroids.

G. Methodology:

After obtaining clearance and approval from the institutional ethics committee and written informed consent of the caregiver, patients admitted to the emergency with organophosphorus compound consumption will be selected after fulfillment of inclusion and exclusion criteria and enrolled in the study(Annexure I).

The eligible patients will be initially subjected to Peradeniya Organophosphorus poisoning scale and will be categorised according to severity.(Annexure IV)

All routine investigations like CBC, RFT, S.Electrolytes, LFT, ECG, RBS, URINE(R/E) will be performed.

Apart from these investigations the other investigations to be done:1.Serum Cholinesterase level2.Serum Creatine kinase level

The serum creatine kinase level will be correlated with the initial Peradeniya clinical scoring and subsequently on day 3 and on discharge.(Annexure V)

H.Statistical analysis:The data obtained will be analysed using 1.Chi square test 2.Analysis of variance 3.Unpaired Student t test

7.3.Does the study require any investigation or interventions to be conducted in patients or animals?if so describe briefly.

Animals: NO

Patients:patient’s caregiver’s written informed consent will be taken.

The following investigations are needed for the study

Complete blood countLiver function test

Renal function testSerum electrolytesRandom blood sugarUrine RoutineECGSerum cholinesteraseSerum creatine kinaseSerum magnesium

7.4.Has the ethical clearance been obtained from ethics committee of your institution in case of 7.3?

“YES”,ethical clearance has been obtained from the ethics committee of our institution.

8.LIST OF REFERENCES:

1. S.B. Agarwal,et al Impairment in Clinical Indices in Acute Organophosphate Insecticide Poisoning Patients in India. The Internet Journal of Toxicology. 2007 Volume 4 Number 1.

2. Kuntal Bhattacharya,Sibaji Phaujdar ,Rathindranath Sarkar and Omar S.Mullick .Serum creatine phosphokinase: A probable marker of severity in organophosphorus poisoning.Toxicol Int 2011 jul-dec;18(2):117-123.

3.Semir Nouira,Fekri Abroug,Souhil Elatrous,Ratik Boujdaria,Slah Bouchoucha.Prognostic value of serum cholinesterase in organophosphate poisoning.Chest 1994;106(6):1811-1814

4.Dilshad A Khan, Mahwish M Bhatti, Farooq A Khan, Syed T Naqvi, Karam A Department

of Pathology, Army Medical College, Int J Clin Exp Med (2008) 274-282.

5.Abdolkarim Pajoumand,Shahin Shadina,Ali Rezaie,Mehboobeh Abdi,Mohammad Abdollahi.Benifits of magnesium sulphate in the management of acute human poisoning by organophosphorus insecticide.Hum Exp Toxicol.2004 dec;23(12):565-569.

6.Paudayal BP .Organophosphorus Poisoning.J Nepal Med Assoc.2008;47(172):251-258.

7.M John,A Oommen,A Zachariah .Muscle injury in organophosphorus poisoning and its role in the development of intermediate syndrome .Neurotoxicology.2003 jan;24(1):43-53

8. Antonio F. Hernández Department of Legal Medicine and Toxicology, University

of Granada School of Medicine, Environmental Research 102 (2006) 70–76.

9.Dursun Aygun,Ali Kemal Erenler ,Ayedin Deniz Karatas,Ahmet Baydin.Intermediate syndrome following Acute Organophosphate poisoning:Correlation with initial Serum levels of Muscle Enzymes.Basic Clin Pharmacol Toxicol 2007;100(3):201-204.

9. Signature of the candidate

10. Remarks of the Guide

11. Name and Designation of

11.1 GuideDr. S.M Goornavar M.D

Associate professor, Department of

General Medicine, SNMC & HSK hospital & RC, Navanagar, Bagalkot.

11.2 Signature

11.3 Head of the Department Dr. S.D Karchi M.D

Professor & HOD, Department of General Medicine, SNMC & HSK hospital & RC, Navanagar, Bagalkot.

11.6 Signature

12. 12.1 Remarks of Chairman and principal

12.2 signature

ANNEXURE IIISTUDY PROFORMA

DATE:

I.P. NO. PATIENT IDENTIFICATION NO.

I.PATIENT INFORMATION:

NAME

AGE

SEX

I.P. NO.

ADDRESS

PHONE No.

OCCUPATION

II.POISONING

COMPOUND

AMOUNT

TIME OF CONSUMPTION

III.SYMPTOMS:

VOMITING

LOOSE STOOLS

SALIVATION/LACRIMATION/SWEATING

DYSPNOEA

BLURRING OF VISION

SEIZURES

LOSS OF CONSCIOUSNESS

IV.PAST HISTORY:

DIABETES MELLITUS

HYPERTENSION

BRONCHIAL ASTHMA/COPD

TUBERCULOSIS

V.PERSONAL HISTORY:

SMOKING

ALCOHOLISM

VI.SYSTEMIC EXAMINATION:

CVS

RS

ABDOMEN

CNS

VII.INVESTIGATIONS:

CBC

LFT

RFT

SE

RBS

URINE(R/E)

ECG

AchE(DAY 1)

ANNEXURE IV PERADENIYA ORGANOPHOSPHORUS POISONING SCALE

PARAMETERS 0 1 2 SCORE

PUPIL SIZE ≥2 mm <2mm PINPOINT

RESPIRATORY RATE

<20/min ≥20/min≥20/min with central cyanosis

HEART RATE >60/min 41-60/min <40/min

FASCICULATION None PresentGeneralised/continuous

Both generalised and continuous

LEVEL OF CONSCIOUSNESS

Conscious and rationale

Impaired response to verbal commands

No response to verbal commands

SEIZURE Absent Present -

GRADE Mild(0-3) Moderate(4-7) Severe(8-11)

ANNEXURE VSERIAL ESTIMATION OF SERUM CREATINE KINASE

DAY 1 DAY 3 ON DISCHARGE

SERUM CK

CLINICAL SCORING

ATROPINE REQUIREMENT

-

COMPLICATIONS IF ANY

-

DURATION OF HOSPITAL STAY

ANNEXURE I

PROFORMA FOR WRITTEN INFORMED CONSENT

Date: Place:

I,Mr/Ms/Mrs , son/daughter/wife of Mr. ,aged about years, have been explained in a language understood by me about the study entitled “STUDY OF LEVEL OF SERUM CREATINE PHOSPHOKINASE AS PROGNOSTIC INDICATOR IN ACUTE ORGANOPHOSPHORUS POISONING” at the Department of General Medicine, S.Nijalingappa Medical College & HSK Hospital and Research Centre, Navanagar, Bagalkot.I have been explained about the procedures and investigations that will be done during this study. I have no objections in sharing my patient’s medical information and details in case records with the investigators of this study. I have been informed that I will not be sharing any incentives. Personal identity will not be revealed and data may be used for publication/dissertation purpose.I understand that my patient’s participation in this study is entirely voluntary and I willfully give consent regarding participation of my patient in this study for the specified duration.

Signature of the caregiver

Relation with the patient Signature of the doctor