Annexure-ii proforma for registration of subjects for dissertation

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1.	NAME OF THE CANDIDATE AND ADDRESS	Dr. POORNIMA.S POST GRADUATE STUDENT, DEPARTMENT OF ANAESTHESIOLOGY, BANGALORE MEDICAL COLLEGE AND RESEARCH INSTITUTE, BANGALORE.
2.	NAME OF THE INSTITUTION	BANGALORE MEDICAL COLLEGE AND RESEARCH INSTITUTE
3.	COURSE OF STUDY & SUBJECT	DOCTOR OF MEDICINE IN ANAESTHESIOLOGY
4.	DATE OF ADMISSION TO THE COURSE	19.8.13
5.	TITLE OF THE TOPIC: COMPARISION OF INDUCTION CHARACTERISTICS OF PROPOFOL VERSUS ETOMIDATE IN PATIENTS UNDERGOING SURGERIES UNDER GENERAL ANAESTHESIA, A BISPECTRAL INDEX GUIDED STUDY.
6. 6.1	BRIEF RESUME OF THE INTENDED WORK NEED FOR THE STUDY: An ideal inducing agent for general anaesthesia should have hemodynamic stability and minimal respiratory side effects. Etomidate is carboxylated imidazole drug with hemodynamic stability , as it has no effect on sympathetic nervous system and baroreceptor functionand has minimal respiratory suppression^1. Propofol decreases blood pressure, cardiac output and systemic vascular resistance by inhibiting sympathetic nervous system and baroreceptor mechanism^2. Bispectral index is an EEG (Electroencephalogram) derived parameter used to assess the depth of anaesthesia. BIS value between 40-60 ensures adequate hypnotic effect during balanced general anaesthesia while improving recovery process. BIS is also known to reduce the doses of drugs required to maintain adequate depth of anaesthesia thereby preventing the possible side effects associated with overuse of anaesthetic agents^3. This study is an attempt to compare the induction characteristics such as hemodynamic parameters and other side effects of both drugs administered in titrated doses to maintain BIS value of 40 - 60 for adequate depth of anaesthesia in order to choose a safe induction agent in patients undergoing surgeries under general anaesthesia.
6.2	REVIEW OF LITERATURE: Moller Peturn et al did a randomized double blinded clinical trial on BIS guided induction of general anaesthesia in 46 patients undergoing major abdominal surgery using propofol and etomidate where one group received propofol infusion at 0.5mg/kg/min and the other group received etomidate infusion at 0.05mg/kg/min and concluded that even with reduced doses of propofol given with the BIS-guided protocol, it often caused significant hypotension^4. A study was conducted by John.M.Gooding and co-authors on effect of etomidate on cardiovascular system on 11 patients with 0.3mg/kg of etomidate. The only significant change noted was, an increase in heart rate by 10% , indicating a stable hemodynamic profile of etomidate^1. Anil.K.Pandey, et al conducted a study on the effect of etomidate and propofol induction on hemodynamics and endocrine response in patients undergoing coronary artery bypass graft surgery on 100 patients with 2mg/kg of propofol and 0.2mg/kg of etomidate and reported that Etomidate provided a safe cardiovascular profile compared to propofol^5. Hashaam B.Ghafoor and co-authors studied on 60 patients undergoing elective surgeries under general anaesthesia with Laryngeal mask airway , the effect of fixed doses of etomidate (0.3 mg/ kg) and propofol (3 mg/ kg) on hemodynamic characteristics and ease of insertion of LMA. They concluded that etomidate reduced the incidence of hypotension following induction than propofol, but may delay the insertion of LMA^6. Heena Parikh and colleagues studied on the utility of bispectral index for titration of propofol dosages and recovery from anaesthesia on 100 patients and concluded that propofol consumed in group who received standard dose of 1.5mg/kg is 2.24 mg/kg whereas its 1.60mg/kg in the group who received a titrated dose of propofol until a BIS value of 45-60 is reached and recovery is 60% in group who received standard propofol dose compared to 86% in BIS guided group, suggesting that BIS guided induction resulted in decrease in dosage of anaesthetic consumed and also aids in speedy recovery^3. Fatma Saricoaglu and associates conducted a study on clinical comparision of etomidate- lipuro, propofol and admixture at induction by infusing the induction agents at the rate of 200 ml/min until BIS value reached 40 and inferred that the hemodynamic parameters were more stable in patients who received etomidate-lipuro and propofol admixture (1:1) and also there are less chances of myoclonus and reduced pain on injection with the use of admixture drug than in patients who received individual induction agents^7. AIM AND OBJECTIVES OF THE STUDY 1. To compare hemodynamic parameters of both drugs. 2. To observe for side effects associated with both drugs during induction.
7 7.1	MATERIAL AND METHODS: SOURCE OF DATA: Study Site Victoria, Vanivilas and Bowring and Lady Curzon Hospitals attached to Bangalore Medical College and Research Institute . Study duration October 2013- May 2015 Study design Prospective randomized double- blind study Sample size . By keeping the confidence limits at 95% and power of study 0.8, to detect 15% difference in mean arterial pressure between the groups , 31 patients need to be included in each group. We have included 35 patients in each group, for better validity. GROUP ‘ P ’: propofol group : 35 GROUP ‘ E ’: etomidate group: 35 TOTAL SAMPLE SIZE: 70 Inclusion criteria 1) ASA physical status I and II patients of 18-50 yrs 2) Patients who gave informed written consent ( annexure 1) Exclusion criteria Patients with cardiovascular and respiratory diseases Patients with chronic abuse of alcohol, drugs, psychotropic agents Patients with hepatic and renal diseases and epilepsy Patients with BMI>30.
7.2	METHOD OF COLLECTION OF DATA: g) Sampling method: After obtaining informed written consent from patients, patients will be randomly divided into 2 groups Group ‘P’ : propofol group – 35 patients Group ‘E’: etomidate group – 35 patients METHODOLOGY : All patients will be kept fasting overnight. Patients will be given Tablet.Alprazolam 0.5mg and Tablet. Ranitidine 150 mg on day before surgery during pre-anaesthetic evaluation. On entering the operation theatre, IV line will be secured. Monitors like Electrocardiogram( ECG), Non-invasive blood pressure monitor( NIBP) and pulse oximeter will be connected. BIS electrodes will be placed and connected to BIS monitors . Patients will be randomly assigned to propofol(P) group and etomidate(E) group. Baseline hemodynamic parameters will be measured. Fentanyl 2microgm/ kg and Midazolam 0.02 mg/kg was given IV. Patients will be preoxygenated with 100% oxygen for 3 minutes.Two minutes after fentanyl administration, infusion of anaesthetic agent will be started. Propofol group will receive propofol at an infusion rate of 0.5mg/kg/min and etomidate group will receive etomidate at an infusion rate of 0.05mg/kg/min. As soon as BIS value reaches 50 , infusion will be stopped and consumed dose of anaesthetic will be recorded individually. Tracheal intubation will be facilitated using vecuronium 0.1 mg/kg and anaesthesia will be maintained as per institutional protocol. Residual neuromuscular blockade will be reversed with neostigmine 0.05mg/kg and glycopyrolate 0.008mg/kg. Trachea will be extubated after adequate recovery of muscle power and patients will be monitored post operatively. PARAMETERS MEASURED: Pulse rate(PR), Systolic blood pressure(SBP), diastolic blood pressure(DBP), mean arterial pressure(MAP), oxygen saturation(spo2) every minute until the infusion of anaesthetic induction agent. Adverse effects such as pain on injection, myoclonus and post operative nausea& vomiting if any. STATISTICAL METHODS TO BE APPLIED For categorical data - Chi- square test or fischer’s exact probability test For nominal data – Student’s t test
7.3	Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so please describe briefly. A) It does not require any intervention on animals. B) Investigations on patients that are routine for the study with their consent.
7.4	Has ethical clearance has been obtained from your institution in case of 7.3? YES
8	LIST OF REFERENCES John.M. Gooding, Guenter Corsenn. Effect of etomidate on cardiovascular system. Anaesth Analgesia 1977;56:717-719. John F.Butterworth, David C.Mackey, John D.Wasnick. Morgan & Mikhail’s clinical anesthesiology, 5^th edition. Lange publications, 2006;186-187. Heena Parikh, Malini Mehta. The utility of Bispectral index for titration of propofol dosages and recovery from anaesthesia. National journal of medical research, dec 2012; vol.2: 484-487. Moller.A. Petrun, Kamenik..M. Bispectral index-guided induction of general anaesthesia in patients undergoing major abdominal surgery using propofol or etomidate, a double- blind randomized clinical trial , 2012;1-9. Anil.K.Pandey, Neeti Makhija, Sandeep Chauhan, Sambhunath Das, Usha Kiran, Akshya Kumar Bisoi et al. The effects of etomidate and propofol induction on hemodynamic and endocrine response in patients undergoing coronary artery bypass graft surgery. World journal of cardiovascular surgery, 2012;2:48-53. Hashaam.B. Ghafoor, Gauhar Afshan, Rehana Kamal. General anaesthesia with laryngeal mask airway : Etomidate and propofol for hemodynamic stability. Open journal of anesthesiology, 2012 ; 2 : 161-165. Fatma Saricoaglu, Sennur Uzun, Oguzhan Arun, Funda Arun, Ulku Aypar. A clinical comparision of etomidate-lipuro, propofol and admixture at induction. Saudi journal of anaesthesia, 2011;5:62-65. Nyman.Y , Von.K. Hofsten, Palm.C , Eksberg.S , .Lonnqvist.P.A . Etomidate – lipuro is associated with considerably less injection pain in children compared with propofol with added lignocaine. British journal of anaesthesia,2006;97:536-39. Christian C. Apfel.Post operative nausea and vomiting.In, Ronald D.Miller(ed). Miller’s Anesthesia, Vol 2,7^th edition. Philadelphia, Churchill Livingstone, Elsevier Inc, 2010;2740 Pierre, Dunkel.M, Rutherford.A et al. Does etomidate increase post operative nausea? A double-blind controlled comparision of etomidate in lipid emulsion with propofol for balanced anaesthesia. European journal of anaesthesiology 2000;17:634- 41. ANNEXURE I INFORMED WRITTEN CONSENT A single randomized double-blind trial to study the Comparision of induction characteristics of propofol versus etomidate in patients undergoing surgeries under general anaesthesia, a bispectral index guided study. You are invited to take part in this research study. The information in this document is meant to help you decide whether or not to take part. Please feel free to ask if you have any queries or concerns.You are being asked to participate in this study being conducted in Department of Anaesthesiology,Victoria hospital/Bowring and Lady Curzon hospital/ Vani Vilas Hospital , Bangalore Medical College and Research Institute because you satisfy our eligibility criteria which are: (1)Age between 18 to 50 years (2)No systemic illness and other co-morbidities You will be one of the 70 patients we plan to recruit in this study. You will be assigned to either of the two study groups. One group of patients will receive standard medications like inj.fentanyl, midazolam, glycopyrolate, neostigmine , succinyl choline along with propofol. The other group will receive standard medications along with etomidate. What is the purpose of research? An ideal inducing agent for general anaesthesia should have hemodynamic stability and minimal respiratory side effects. Etomidate is a cardio stable drug with minimal respiratory suppression . Propofol decreases blood pressure and cardiac output. This study is an attempt to compare the induction characteristics of both drugs in order to choose a safe induction agent in general anaesthesia.We have obtained permission from the Institutional Ethics Committee for conducting this study. Possible risks to you The study drug etomidate may lead to myoclonus, pain on injection and post operative nausea and vomiting. Propofol causes green coloured urine and involuntary movements during induction. Possible benefits to you You are not expected to get any benefit from being on this research study, other than the treatment benefit and free investigations/tests. Possible benefits to other people The results of the research may provide benefits to the society in terms of advancement of medical knowledge and/or therapeutic benefit to future patients. The alternatives you have If you do not wish to participate, you have the alternative of getting the standard treatment for your condition. Confidentiality of the information obtained from you You have the right to confidentiality regarding the privacy of your medical information (personal details, results of physical examinations, investigations, and your medical history). By signing this document, you will be allowing the research team investigators, other study personnel, institutional ethics committee, if required.The results of clinical tests and therapy performed as part of this research may be included in your medical record. The information from this study, if published in scientific journals or presented at scientific meetings, will not reveal your identity. How will your decision to not participate in the study affect you? Your decision not to participate in this research study will not affect your medical care or your relationship with the investigator or the institution. Your doctor will still take care of you and you will not lose any benefits to which you are entitled. Contact persons For further information/questions,you can contact us at the following address Dr. Nethra.S.S, Professor,Department of Anaesthesiology,BMC&RI Dr.Poornima.S ,PG student,Department of Anaesthesiology,BMC&RI I, Mr/Mrs/Ms ,exercising my own free willpower of choice, hereby give consent for myself as an object in the clinical study “COMPARISION OF INDUCTION CHARACTERISTICS OF PROPOFOL VERSUS ETOMIDATE IN PATIENTS UNDERGOING SURGERIES UNDER GENERAL ANAESTHESIA , A BISPECTRAL INDEX GUIDED STUDY.”conducted by Dr.Nethra..S.S , Dr.Poornima.S , Department of Anaesthesiology, Victoria hospital/ Bowring and Lady Curzon hospital/ Vanivilas hospital, Bangalore Medical college and Research Institute. The attending doctors have informed me to my satisfaction and in a language best understood by me, the purpose of this study, the materials to be used during the course of this study as well as the side effects/ complications associated with the methods/tools to be used. I shall not hold the doctors or the staff responsible for any untoward consequences. I am also aware of my right to opt out of the study without prejudice to further treatment at any time during the course of the study without having to give any reasons to do so. Signature of attending doctor : Date : Signature/Left thumb impression of patient Signature of witness : ANNEXURE –2 : MYOCLONUS GRADING 0 - no myoclonus 1-minor myoclonus 2- moderate myoclonus 3- severe myoclonus   ANNEXURE -3 : PAIN GRADING SCALE 0- no pain 1-verbal complain of pain 2-withdrawal of arm 3- both verbal complain and withdrawal of arm. Pain will be assessed during the infusion of the induction agent ANNEXURE-4 : Post operative nausea & vomiting VRS(Verbal Rating Scale) For Nausea:- 0-No nausea 1-mild nausea 2-moderate nausea 3-severe nausea For Vomiting : Nil-no vomiting Mild-1 episode Moderate-2 or 3 episodes Severe- more than 3 episodes Nausea and Vomiting will be evaluated postoperatively as early (0 to 6 hrs) and late (6 to 24hrs). Patients with vomiting in the post operative period will receive inj. Ondansetron 4mg intravenously as rescue antiemetics.