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CTRI Number  CTRI/2018/05/014307 [Registered on: 31/05/2018] Trial Registered Retrospectively
Last Modified On: 22/05/2018
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Surgical/Anesthesia 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   Comparison of different drug combinations with respect to changes in pulse rate and blood pressure during induction of anaesthesia. 
Scientific Title of Study   Comparison of the haemodynamic responses to laryngoscopy and intubation on induction with Etomidate, Propofol-Ketamine or Propofol-Etomidate 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Malvika Gupta 
Designation  Post graduate resident 
Affiliation  Maulana Azad Medical College 
Address  Department of Anaesthesiology and Intensive care, BL Taneja Block, 3rd Floor, Maulana Azad Medical College, Bahadur shah zafar marg, New Delhi
Department of Anaesthesiology and Intensive Care. BLT block, 3rd floor. Maulana Azad Medical College. Bahadur Zafar Marg. New delhi-110002
Central
DELHI
110002
India 
Phone  9953213355  
Fax    
Email  drmalvika2910@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr UC Verma 
Designation  MD, Director Professor and HOD, Department of Anaesthesiology 
Affiliation  Maulana Azad Medical College 
Address  Department of Anaesthesiology and Intensive Care. BLT block, 3rd floor. Maulana Azad Medical College. Bahadur Zafar Marg. New delhi-110002
Department of Anaesthesiology and Intensive Care. BLT block, 3rd floor. Maulana Azad Medical College. Bahadur Zafar Marg. New delhi-110002
Central
DELHI
110002
India 
Phone  9968604211  
Fax    
Email  ucverma2k@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Malvika Gupta 
Designation  Post graduate resident 
Affiliation  Maulana Azad Medical College 
Address  Department of Anaesthesiology and Intensive Care. BLT block, 3rd floor. Maulana Azad Medical College. Bahadur Zafar Marg. New delhi-110002
Department of Anaesthesiology and Intensive Care. BLT block, 3rd floor. Maulana Azad Medical College. Bahadur Zafar Marg. New delhi-110002
Central
DELHI
110002
India 
Phone  9953213355  
Fax    
Email  drmalvika2910@gmail.com  
 
Source of Monetary or Material Support  
Maulana Azad Medical College 
 
Primary Sponsor  
Name  Malvika Gupta 
Address  Department of Anaesthesiology and Intensive Care. BLT block, 3rd floor. Maulana Azad Medical College. Bahadur Zafar Marg. New delhi-110002 
Type of Sponsor  Other [Self] 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Malvika Gupta  Lok Nayak Hospital   Operation theatre, Department of anaesthesiology and intensivecare
Central
DELHI 
9953213355

drmalvika2910@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Ethics Committee associated with Maulana Azad Medical College  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Patients undergoing elective procedures under general anaesthesia requiring endotracheal intubation.,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Etomidate  Etomidate 0.3 mg/kg for induction of anaesthesia 
Intervention  Propofol and Etomidate  Etomidate 0.15 mg/kg followed by Propofol 1 mg/kg for induction of anaesthesia. 
Intervention  Propofol and Ketamine  Ketamine 1 mg/kg followed by Propofol 1 mg/kg for induction of anaesthesia  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  50.00 Year(s)
Gender  Both 
Details  ASA Physical status 1 and 2 patients 
 
ExclusionCriteria 
Details  Known history of hypersensitivity to etomidate, propofol or ketamine, egg or soya; BMI>30 kg/sq.m; History of postural hypotension, diabetes mellitus, cardiovascular diseases; GERD; Pregnancy; Anticipated difficult airway 
 
Method of Generating Random Sequence   Random Number Table 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Participant Blinded 
Primary Outcome  
Outcome  TimePoints 
Mean Arterial Pressure  Baseline; After midazolam and Fenatnyl; after induction agent; just prior to laryngoscopy; 1,2,3,4,5,7 and 10 minutes after intubation. 
 
Secondary Outcome  
Outcome  TimePoints 
1. Systolic and diastolic blood pressure
2. Changes in heart rate
3. BIS values
4. Requirement for rescue intervention. 
Baseline; After midazolam and Fenatnyl; after induction agent; just prior to laryngoscopy; 1,2,3,4,5, 
 
Target Sample Size   Total Sample Size="90"
Sample Size from India="90" 
Final Enrollment numbers achieved (Total)= "90"
Final Enrollment numbers achieved (India)="90" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   02/01/2017 
Date of Study Completion (India) 02/03/2018 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="2"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   none yet 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary  

The induction of general anaesthesia is often accompanied by significant haemodynamic changes especially hypotension. On the other hand, laryngoscopy and endotracheal intubation are potent noxious stimuli which provoke untoward haemodynamic responses such as hypertension and tachycardia, which can be detrimental in patients with poor myocardial reserve. Such variations in haemodynamic parameters may alter the fine balance between myocardial oxygen supply and demand, thus accelerating myocardial ischemia. Therefore, preserving haemodynamic stability during anaesthesia induction is of vital importance.

Endotracheal intubation remains the gold standard for securing the airway during general anaesthesia. In 1940, Reid and Brace first described the haemodynamic response to laryngoscopy and intubation. The circulatory perturbations stem from reflex sympathetic discharge due to epipharyngeal and laryngopharyngeal stimulation, and are marked by a rise in circulating plasma adrenaline and noradrenaline concentrations with consequent increases in arterial blood pressure, heart rate and oxygen consumption. The rise in pulse and blood pressure are usually transitory, variable and unpredictable and are usually well tolerated by healthy individuals. However, these above mentioned effects may have untoward consequences in high-risk patients like those with hypertension, heart disease and coronary artery disease and may lead to significant haemodynamic changes such as dysrhythmias, hypertension, myocardial ischaemia, infarction and also hypoxia, hypercapnia, laryngospasm and bronchospasm. Other rare side effects include an increase in intracranial and intra-ocular pressures.

In an attempt to find the ideal intravenous induction agent which provides haemodynamic stability, many induction agents have been studied and used over the last decades. Although the evolution of induction agents continues, till date no ideal induction agent has yet been identified which is able to provide haemodynamic stability with minimal side effects.

Propofol (2, 6 di-isopropylphenol) is an ultra-short-acting sedative-hypnotic agent, widely used for the induction of general anaesthesia. The major disadvantages of rapid induction with propofol are impaired cardiovascular and respiratory function which may put patients at risk of hypotension, bradycardia, and apnea. Etomidate, another intravenous anaesthetic induction agent, possesses unique desirable properties such as a rapid onset and short duration of action, relative cardiovas­cular and respiratory stability, as well as neuroprotec­tive effects, making it an attractive induction agent to facilitate intubation whenever haemodynamic stability is required. However, besides myoclonus, pain on injection and nausea and vomiting, a rare side effect of this drug is profound and persistent, dose dependent adrenocortical suppression by reversible inhibition of mitochondrial 11 β-hydroxylase enzyme of the adrenal steroid synthesis pathway which may be seen even after the administration of a single bolus of etomidate.  Studies have also shown that administration of etomidate for induction of anaesthesia may lead to postoperative vasopressor dependency, as well as substantially unfavourable outcomes such as mortality, cardiovascular morbidity and prolonged hospital stays. Ketamine is another short-acting general anaesthetic with distinct cardiovascular effects. Unlike most anaesthetic agents, it stimulates the cardiovascular system through catecholamine release. This is character­ized by an increase in heart rate, blood pressure and cardiac output. Thus, all these agents have some side effects which seem to be dose dependent.

Lately, the simultaneous administration of different anaesthetic agents (co-induction) for  the induction of anaesthesia has been suggested and may offer distinct advantages over monotherapy. In the past, many studies have compared the combinations of various anaesthetic induction agents such as etomidate, ketamine and propofol, but studies comparing the combinations of propofol- etomidate and propofol- ketamine are limited. Also, most studies comparing the haemodynamic effects of induction agents have been performed without monitoring the depth of anaesthesia, which raises the question as to what extent the observed differences in the haemodynamic effects of the anaesthetic agents were related to the differences in the depth of anaesthesia.

The unfavourable side effect profile of etomidate prompts the search for agents or combination of agents which can provide comparable or more favourable haemodynamic stability. Co-induction can be used for the induction of anaesthesia in pa­tients using combinations of some anaesthetic agents with opposing cardiovascular effects. Ketamine and etomidate are both drugs which maintain the blood pressure and can be used with propofol to reduce the degree of hypotension associated with the use of propofol. Theoretically, the divergent haemodynamic effects of propofol and ketamine might be neutralizing and thus reduce the incidence of overall adverse effects. Mixtures of ketamine and propofol are popularly used as an admixture called ketofol. Similarly, the haemodynamic consequences of propofol may be minimized by combining it with etomidate in order to maintain haemodynamic stability and minimize the adverse effects of either drug when used alone. There is paucity in literature on studies comparing the combinations of propofol-etomidate and propofol-ketamine as induction agents on the haemodynamic responses to laryngoscopy and endotracheal intubation.

Considering the clinical importance of attenuating the haemodynamic responses to laryngoscopy and endotracheal intubation and the paucity of literature comparing etomidate and combinations of propofol- ketamine and propofol- etomidate as induction agents, we aimed to compare the effects of these three groups in maintaining haemodynamic stability during induction and following endotracheal intubation in elective surgery.

 
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