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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1.
NAME OF THE CANDIDATE
AND ADDRESS
2.
NAME OF THE INSTITUTION
3.
COURSE OF STUDY & SUBJECT
4.
DATE OF ADMISSION TO THE
COURSE
5.
6.
Dr. RITU JOSE
POST GRADUATE STUDENT
DEPARTMENT OF ANAESTHESIOLOGY,
BANGALORE MEDICAL COLLEGE &
RESEARCH INSTITUTE,
BANGALORE – 560002.
BANGALORE MEDICAL COLLEGE AND
RESEARCH INSTITUTE
DOCTOR OF MEDICINE IN
ANAESTHESIOLOGY
01 - 06 – 2012
A STUDY TO COMPARE THE EFFICACY
OF PRETREATMENT WITH
TITLE OF THE TOPIC:
INTRAVENOUS MAGNESIUM SULPHATE
WITH PLACEBO DURING INDUCTION OF
.
ANAESTHESIA WITH PROPOFOL IN THE
REDUCTION OF SUCCINYLCHOLINE
INDUCED FASCICULATIONS AND
MYALGIA
BRIEF RESUME OF THE INTENDED WORK
6.1 NEED FOR THE STUDY:
Succinylcholine is considered to be the best drug for providing ideal intubating conditions.
However, its usefulness is limited by the frequent occurrence of postoperative myalgia.
Fasciculation may be observed in 95% of patients, but the incidence of myalgia at 24 h is about
50% following use of succinylcholine [1] Although self-limiting, it is generally agreed that
postoperative myalgia is unacceptable in modern anaesthetic practice
The pathophysiology of succinylcholine induced myalgia is poorly understood. Hence there
is no standard treatment available for the same. Different pre-treatment modalities have been
advocated to reduce the incidence and severity of fasciculations and myalgia including nondepolarizing neuromuscular blockers, [2] intravenous lignocaine, [3] nonsteroidal antiinflammatory
drugs (NSAIDs)[4] etc
Magnesium competes with calcium at the pre-synatic end plate of neuromuscular junction
and inhibits the release of acetylcholine from the motor nerve terminal, and, to a lesser extent,
decreases the sensitivity of the postjunctional membrane and reduces the excitability of the
muscle fiber.[5], [6] . Magnesium has been shown to abolish fasciculations[7] following the use of
succinylcholine though its role in reduction of myalgia is questionable.
This study attempts to compare the efficacy of pretreatment with magnesium sulphate with
placebo during propofol induction in reducing the incidence and severity of succinylcholine
induced fasciculations and myalgia
6.2 REVIEW OF LITERATURE:
Shreiber and colleagues conducted a metaanalysis of 52 randomised controlled trials
attempted at prevention of succinylcholine induced fasciculations and myalgia .Some of the
conclusions drawn include, the incidence of succinylcholine induced myalgia is high, and
symptoms sometimes last for several days. Higher doses of succinylcholine decrease the risk of
myalgia compared with lower doses and induction agents thiopentone as well as propofol do have
a role in reducing myalgia. There is no clear relation between succinylcholine related
fasciculation and myalgia. Finally origin of myalgia is likely to be multifactorial, and it may be
naive to believe that one single drug can completely prevent it. The most effective prevention may
be with a drug combination. [1]
Mahendra et al, in their study concluded that intravenous magnesium sulfate 40 mg/kg
when used with propofol for induction of anesthesia significantly reduced the incidence and
severity of succinylcholine induced fasciculations and myalgia. [8]
Stacey and colleagues studied the effects of magnesium sulphate on succinylcholine induced
complications during rapid sequence induction of anaesthesia with thiopentone. They observed
that the incidence of fasciculations was significantly lower in the patients pretreated with
magnesium in comparison to control group whereas there was no difference between the groups
in the incidence of myalgia after surgery [9]
Aldrete JA et al, studied the changes in serum potassium in 60 patients following
administration of succinylcholine and came to the conclusion that patients who were pretreated
with intravenous magnesium sulphate did not show the increase in serum potassium that was
observed in the control group. [10]
Kararmaz A. and colleagues through their study on high dose propofol demonstated
evidence that administration of propofol in the dose of 3.5 mg/kg body weight was effective in
the reduction of both the incidence and severity of succinyl choline induced myalgia and
fasciculations. [11]
Hence our attempt in studying the efficacy of pretreatment with magnesium sulfate during
propofol induction of anesthesia on the incidence and severity of succinylcholine induced
fasciculations and myalgia is justified.
6.3
AIM AND OBJECTIVES OF THE STUDY:
1) To investigate whether pretreatment with magnesium sulfate during induction of anaesthesia with propofol
could reduce the incidence and severity of succinylcholine induced fasciculations and myalgia .
2) To study the side effects of the magnesium sulphate if any.
7
MATERIAL AND METHODS:
7.1
SOURCE OF DATA:
Patients undergoing elective surgery under general anaesthesia in Victoria hospital,
AAAaVani Vilas Hospital and Bowring and Lady Curzon Hospitals attached to
aaaaaaBangalore Medical College and Research Institute .
7.2
METHOD OF COLLECTION OF DATA:
a) Study Duration
The study will be done between November 2012 to October 2014
b) Design Of Study
Prospective, double blind, randomised control clinical trial.
c) Site of Study
Victoria hospital, VaniVilas Hospital and Bowring and Lady Curzon Hospital attached to
aaaBangalore Medical College and Research Institute, Bangalore .
d) Sample Size
The sample size calculation was based on an assumption that the incidence of
fasciculations and postoperative myalgia was 95% and 50% respectively. Interventions which
decrease the incidence to 35% would be of interest. [12] The study required 15 patients in each
group for a power of 80% (β=80% and α=0.05) . However 60 patients classified as per American
Society of Anesthesiologists (ASA annexure I) classes I and II, in the age group of 18-50 years,
scheduled for elective surgery under general anaesthesia will be studied to increase the validity of
results. The patients will be randomly allocated into two groups of 30 each.
Magnesium sulphate group (Group M,n=30) and Control group(Group C ,n=30) .
e) Inclusion criteria:
1) Patients who give informed written consent.(annexure II)
2) Patients aged between 18 to 50 years.
3) Patients belonging to ASA Class I and Class II(annexure I)
f) Exclusion criteria:
1) Patients with pre-existing musculoskeletal disorders
2) Patients taking calcium channel blockers
3) Subjects who had received analgesics within 24 h before scheduled surgery
4) Patients receiving sedatives other than those determined by the study protocol
5) Patients who are hypersensitive to any of the drugs in the study
6) Patients with renal dysfunction
g) Sampling method:
After obtaining informed written consent from patients, patients will be randomly divided
into 2 groups by draw of lots.
Group M : Magnesium Sulphate group – 30 patients
Group C: Control group – 30 patients
Before induction the patients of Group M will be pretreated with Inj. Magnesium sulfate 40
mg/kg body weight diluted to 20 ml with normal saline, while patients of Group C will be
administered 20 ml of Normal saline intravenously over a period of 10 min. Patients will be
monitored with electrocardiography, oxygen saturation, non invasive blood pressure.
All patients will receive standard premedication with Inj. Midazolam 2mg, Inj. Glycopyrrolate
0.2 mg , and Inj Fentanyl 50 mcg intravenously. After preoxygenating with 100%oxygen, all
patients will be induced with Inj Propofol 2 mg/kg body weight, followed by administration of
Inj Succinylcholine 2 mg/kg. Fasciculations will be evaluated by a blinded observer and will be
graded as follows: [4]
0-
Nil ( no visible fasciculations)
1-
Mild ( fine fasciculations at the eyes, neck, face or fingers without limb movement)
2-
Moderate (fasciculations appearing bilaterallty or obvious limb movements )
3-
Severe (widespread sustained fasciculations)
Oral endotracheal intubation will be performed after assessing complete muscular
relaxation. Anaesthesia will be maintained with oxygen in 50% nitrous oxide and Isoflurane 12%. IV Vecuronium 0.02mg/kg will be used for maintenance of muscle paralysis At the end of
surgery, neuromuscular blockade will be reversed with Inj Neostigmine 2.5 mg and
Inj.Glycopyrrolate 0.4mg. Trachea will be extubated after adequate recovery of muscle power.
Myalgia is defined as "muscle pain not related to surgical intervention". The incidence and
severity of myalgia will be recorded by a blinded observer for the next 24 h of surgical
intervention. Myalgia will be graded as follows : [13]
0 - No pain
1 – Pain at one site without functional disability
2 – Pain involving more than one site without functional disability
3 – Pain involving more than one site with functional disability
During the post operative period , in addition to myalgia , the patient’s heart rate, blood pressure ,
oxygen saturation, respiratory rate and urine output will also be monitored. Any intraoperative
and postoperative side effects and complications will be noted.
Statistical evaluation of data will be done as follows:
1) For categorical data – Chi square test or Fischer’s exact probability test
2) 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 only 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:
1. Schreiber J, Lysakowski C, Fuchs-Buder T, Tramer MR. Prevention of succinylcholine
induced Fasciculations and myalgia. A Meta Analysis of randomized trials. Anesthesiology
2005;103:877-84.
2. O'Sullivan EP, Williams NE, Calvey TN. Differential effects of neuromuscular blocking agents
on suxamethonium induced fasciculations and myalgia. Br J Anaesth 1988;60:367-71.
3. Raman SK, San WM. Fasciculations, myalgia and biochemical changes following
succinylcholine with atracurium and lidocaine pretreatment. Can J Anaesth1997;44:498-502.
4. Kahraman S, Ercan S, Aypar U, Erdem K. Effect of preoperative I.M. administration of
diclofenac on suxamethonium-induced myalgia. Br J Anaesth 1993;71:238-41.
5. Jekinson DH .The nature of the antagonism between calcium and magnesium ions at the
neuromuscular junction. J Physiol (Lond) 1957;138:43-4.
6. David B. Glick .The Autonomic Nervous System . In, Ronald D.Miller(ed). Miller’s
Anaesthesia, 7th edition. Philadelphia, Churchill Livingstone, Elsevier Inc, 2010; Pp292
7. Minerals and Electrolytes . In, Robert K. Stoelting, Simon C. Hillier (ed). Pharmacology and
Physiology in Anaesthetic Practice, 4th edition.Philadelphia, Lippincott Williams & Wilkins,
2006; 619
8. Mahendra Kumar, Nalin Talwar, Ritu Goyal, Usha Shukla, AK Sethi. Effect of magnesium
sulfate with propofol induction of anesthesia on succinylcholine induced fasciculations and
myalgia .J Anaesthesiol Clin Pharmacol. 2012;28(1) :81-85
9. Stacey MR, Barclay K, Asai T, Vaughan RS. Effect of magnesium sulphate on suxamethonium
induced complication during rapid sequence induction of anaesthesia.Anaesthesia1995;50:933-6
10.Aldrete JA, Zahler A, Aikawa JK. Prevention of succinylcholine-induced hyperkalaemia by
magnesium sulfate. Can Anaesth Soc J 1970; 55: 477–84
11. Kararmaz A, Kaya S, Turhanoglu S, Ozyilmaz MA. Effects of high-dose propofol on
succinylcholine induced fasciculations and myalgia. Acta Anaesthesiol Scand 2003;47:180-4
12. CK Pandey, M Tripathi , G Joshi , ST Karna , N Singh , PK Singh. Prophylactic use of
gabapentin for prevention of succinylcholine induced fasciculation and myalgia: A randomized,
double-blinded, placebo-controlled study. J Anaesthesiol Clin Pharmacol 2011;58: 19-22
13. White DC. Observations on the prevention of muscle pains after suxamethonium. Br J
Anaesth 1962; 34:332-5
9.
SIGNATURE OF THE
CANDIDATE
(Dr. RITU JOSE )
REMARKS OF THE GUIDE
The study has beneficial effects on the patient
outcome
11.1
NAME AND
DESIGNATION
OF GUIDE
Dr. HARSOOR S.S.
Professor
Department of Anaesthesiology
BMC&RI
11.2
SIGNATURE
11.3
CO-GUIDE ( IF ANY )
11.4
SIGNATURE
11.5
HEAD OF THE
DEPARTMENT
11.6
SIGNATURE
10.
11.
Dr. T.N. SRIKANTA MURTHY
Professor and Head
Department of Anaesthesiology
BMC&RI
12.1
REMARKS OF THE
CHAIRMAN AND
PRINCIPAL
12.2
SIGNATURE
Dr. O.S.SIDDAPPA
Director and Dean,
Bangalore Medical College and Research Institute,
Bangalore.