RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES BANGALORE, KARNATAKA

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION .

1. NAME OF THE CANDIDATE Dr. GEETHA S.M. AND ADDRESS POST GRADUATE STUDENT, DEPARTMENT OF ANAESTHESIOLOGY, BMC & RI BANGALORE

2. NAME OF THE BANGALORE MEDICAL COLLEGE AND INTSITUTION RESEARCH INSTITUTE

3 COURSE OF STUDY AND DOCTOR OF MEDICINE IN SUBJECT ANAESTHESIOLOGY.

4. DATE OF ADMISSION TO 14.08.2012. THE COURSE.

5. TITLE OF THE TOPIC; TO COMPARE THE EFFECT OF IV MAGNESIUM PRETREATMENT ON SPEED OF ONSET AND DURATION OF ACTION OF ATRACURIUM AND RECOVERY FROM NEUROMUSCULAR BLOCKADE.

6.0 BRIEF RESUME OF THE INTENDED WORK: 6.1 NEED FOR THE STUDY

Magnesium is widely used in obstetrics for prophylaxis and treatment of convulsions in parturient with preeclampsia.(1) Studies have shown that when used as pretreatment in General Anaesthesia(GA), Magnesium exhibits anesthetic, analgesic and muscle relaxation effects.(2) Magnesium suppresses the peripheral neuromuscular transmission by decreasing the acetyl choline release from motor nerve endings. Magnesium is known to enhance the effects of nondepolarizing neuromuscular blocking drugs.(1) Pre and intraoperative administration of Magnesium sulphate was known to reduce the anesthetic drug requirement in General Anaesthesia.(3)

6.2 REVIEW OF LITERATURE Guptha.K, Vohra V, Sood J studied the role of Magnesium sulphate as an adjuvant during general anaesthesia and concluded that Magnesium sulphate has anaesthetic, analgesic and muscle relaxation effects and significantly reduces the anesthetic drug requirement(2). A study on the effects of Magnesium sulphate in reducing intraoperative anesthetic requirement was conducted by Telei L, Esen F and coworkers,and J.H Ryu& others and concluded that administration of Magnesium sulphate led to a significant reduction in the requirement for anaesthetic drug during total IV anaesthesia with propofol, remifentanil and vecuronium(3,4)

Aissaoui, Younes and others found that the addition of Magnesium sulphate to propofol and fentanyl improved intubating conditions without administration of Neuromuscular blocking drugs(5.Similar observations were also made by Puri G.D and others in patients with coronary artery disease(6). D.H.Lee and I.C. Kwon observed that preoperative IV Magnesium sulphate attenuated BIS and hypertensive episodes during the pre delivery period, hence recommended Magnesium sulphate as an adjuvant during GA for CS to avoid perioperative awareness and pressor responses(7).

Wu Hong-Liang, YE Tie-hu SUN Li studied the effects of Atracurium Pre treatment with Magnesium sulphate on speed of onset, duration and recovery of Neuromuscular blockade. They concluded that, prior administration of Magnesium sulphate can increase the speed of onset of Atracurium and prolong the duration of Atracurium induced neuromuscular blockade(8).

The effects of Magnesium sulphate pretreatment on onset and recovery characteristic of cisatracurium were studied by Sang Hun Kin and coworkers. They concluded that Magnesium sulphate resulted in 29% shortening of onset time of cisatracurium without prolonging the recovery of neuromuscular block(9).

6.3 AIM AND OBJECTIVES OF THE STUDY:

1. To assess the intubating conditions following Inj Atracurium after pre treatment with Magnesium sulphate.

2. To study the speed of onset, duration of action and recovery from neuromuscular blockade.

7.0 MATERIAL AND METHODS: 7.1 SOURCE OF DATA

Patients undergoing surgeries under General Anesthesia at Victoria Hospital, Vani Vilas Hospital and Bowring and Lady Curzon Hospital attached to Bangalore Medical College and Research Institute, Bangalore are divided into two group of 30 patients each.

7.2 METHOD OF COLLECTION OF DATA

a) Design of study: Prospective randomized double blinded controlled clinical trial.

b) Study duration:The study will be conducted between November 2012 to October 2014

c)Place of Study: Victoria Hospital, Vani Vilas Hospital and Bowring and Lady Curzon Hospital attached to BMC&RI.

d) Sample Size : By keeping the confidence limits at 95% and power of study at 80%, to detect 20% difference in recovery time between two groups, minimum sample size required is 10 in each group. We have included 30 patients belonging to ASA Grade I and II in each group to have higher validity.

e) Inclusion Criteria: 1) Patients aged between 18 and 50 years. 2) Patients scheduled for surgery under General Anesthesia. 3) Patients belonging to ASA Grade-I and II.(Annexure-I) f) Exclusion Criteria: 1) Patients suffering from CNS disorders. 2) Patients with Neuromuscular Diseases. 3) Patients receiving medications known to influence neuromuscular function (eg. calcium channel blockers, phenytoin, aminoglycosides).

METHODOLOGY:

(g) Sampling method: After obtaining informed and written consent (annexure-II) from patients, patients are randomly assigned to Group M-Magnesium group and Group C - Control group.

Group M.: Study Group 30 patients Group C: Control Group 30 patients Total sample size:- 60 patients

All patients will be premedicated with inj Midazolam 2mg IV and monitored for non invasive blood pressure(NIBP), electrocardiography(ECG) and pulse oximetry (SpO2). Before induction of GA, patients in Magnesium group received Magnesium sulphate 1.5gm in 50ml of Normal saline over 5 min at the rate of 10ml/min as IV infusion and patients in control group received the same volume of normal saline. After infusion, all patients will be preoxygenated with 100% O2 for 3 min and Anesthesia induced with inj propofol 100mg + inj fentanyl 100microgm+ inj atracurium 0 .5 mgs/ kg body wt.

Neuromuscular function will be assessed by Train of four (TOF) responses on the side opposite to BP Cuff. Trachea intubated 90 seconds after administration of Atracurium. Intubation quality will be assessed as per Goldberg and colleagues grading of intubating conditions(10) [annexure- III], and Onset time (OT), Total Duration (TD) and recovery time (RT) of neuromuscular blockade were recorded. Hemodynamic parameters following induction and intubations will be recorded and analysed.

Parameters to be observed:- 1.Pulse rate(PR), systolic blood pressure(SBP), diastolic blood pressure(DBP), mean blood pressure(MBP), oxygen saturation(SpO2) readings recorded before induction(baseline value), after induction and after intubation till the end of surgery.

2.Train of four(TOF) responses following induction, during intubation until the satisfactory reversal of neuromuscular blockade.

h) Statistical Analysis: Statistical evaluation of data or parameters will be done as follows:

 Chi squre test for categorical data.  Student ‘t’ test for nominal data.

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 is 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 : 1. Robert K Stoelting, Simon C. Hillier. Minerals and electrolytes. In pharmacology and physiology in anaesthetic practice. 4th edition philidelphia, Lippincott, Williams and Wilkins; 2006: 618-620.

2.Gupta K, Vohra V, Sood J, The role of Magnesium sulphate as an adjuvant during general Anaesthesia. Anaesthesia.2006 ; 61(11):1058-63. 3 Telei L, Esen F, Akcora D, Erden T, Canbolat AT, Akpir K. Evaluation of effects of Magnesium sulphate in reducing intraoperative anaesthetic requirements. Br J Anaesth,2002;89(4):594-8 4. J H Ryu, M H Kang, K S Park. Effecs of magnesium sulphate on intraoperative anesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia.Br J Anaesth 2008;100(3):397-403.

5. Aissaoui, Younes; Qamous, Youssef; Serghini, Issam; Zoubir, Mohammed; Salim, Jaafar Lalaoui; Boughalem, Mohammed. Magnesium sulphate as an adjuvant to tracheal intubation without muscle relaxation. European Journal of Anaesthesiology:2012; 29(8):391-397. 6. Puri GD, Marudhachalam KS,Chari P, Suri RK.The effect of Magnesium sulphate on hemodynamics and its efficacy in attenuating the response to endotracheal intubation in patients with coronary artery disease. Anesth Analg.1998;87(4):808- 811.

7. D.H. Lea and I.C. Kwon. The beneficial effects of Magnesium sulphate as an adjuvant during GA for CS.Br J Anaesth. 2009 ;103(6):861-6

8.WuHong Liang, YE Tie-Lu, SUN Li. Effects of Atracurium pretreatment with Magnesium on speed of onset, duration, and recovery of Neuro muscular blockade. .Acta Acad Med Sin,2009,31(1):73-76 9 .Sang Hue Kin,Keum-Young So,Ki-Tae Jung.Effect of Magnesium sulphate pretreatment on onset and recovery characteristics of Cisatracurium..Korean J Anesthesiol.2012 ;62(6):518-23.

10.Goldberg ME, Lariani GE, Azad SS, Sosis M, Seltzer,Ascher J. Comparision of tracheal intubating conditions and neuromuscular blocking profiles after intubating doses of mivacurium chloride or succinylcholine in surgical outpatients.Anesth Analg 1989;69:93-99.

9. SIGNATURE OF THE CANDIDATE

(Dr. GEETHA S M)

10. REMARKS OF THE GUIDE The study helps in optimized use of muscle relaxants in surgical patients

11.1 NAME & DESIGNATION OF Dr. HARSOOR S S GUIDE Professor, Department of Anaesthesiology BMC & RI. 11.2 SIGNATURE

11.3 CO – GUIDE (IF ANY)

11.4 SIGNATURE

11.5 HEAD OF THE DEPARTMENT Dr. T.N. SRIKANTA MURTHY, Professor and Head, Department of Anaesthesiology, 11.6 SIGNATURE BMC&RI.

12.1 REMARKS OF THE CHAIRMAN & Dr. O.S.SIDDAPPA PRINCIPAL Director and Dean, Bangalore Medical College and 12.2 Research Institute, Bangalore. SIGNATURE