Comparison of different drug combinations with respect to changes in pulse rate and blood pressure during induction of anaesthesia.

Phase 3

Completed

Conditions: Patients undergoing elective procedures under general anaesthesia requiring endotracheal intubation.

Registration Number: CTRI/2018/05/014307

Lead Sponsor: Malvika Gupta

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 cardiovasÂcular and respiratory stability, as well as neuroprotecÂtive 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 Î²-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 characterÂized 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 paÂtients 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 90

Inclusion Criteria

ASA Physical status 1 and 2 patients.

Exclusion Criteria

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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Measures

Name	Time	Method
1. Systolic and diastolic blood pressure	2. Changes in heart rate

Trial Locations

Locations (1): Lok Nayak Hospital
🇮🇳
Central, DELHI, India
Lok Nayak Hospital
🇮🇳Central, DELHI, India
Malvika Gupta
Principal investigator
9953213355
drmalvika2910@gmail.com