European Journal of Cardiovascular Medicine

General anaesthesia (GA) is the state produced when a patient receives medications to produce amnesia and analgesia with or without reversible muscle paralysis”. One way to conceptualize a patient under anaesthesia is as someone in a regulated, reversible unconscious condition. [1] Anaesthesia makes it possible for a patient to undergo surgery that would otherwise cause excruciating pain, amplify severe physiologic exacerbations, and leave them with bad memories. [1] Induction phase is utilized to induce anaesthesia and quick unresponsiveness. John Lundy presented the first instance of thiopental usage in 1934. [1] While many pharmacologic groups of medications are employed now these days, the most often utilized agent for this purpose is etomidate. [2]

[2] Induction agents are medications that, when administered intravenously at the proper dose, quickly induce unconsciousness. induction agents are used to induce anaesthesia prior to the other drugs being given to maintain anaesthesia for longer procedure by intravenous infusion to provide conscious sedation during procedures undergoing in local anaesthesia and intensive care units. [3] An ideal induction agent for general anaesthesia should have hemodynamic stability, minimal respiratory side effect, rapid clearance with minimal side effects and drug interactions. [4] Etomidate, propofol, thiopental, midazolam, ketamine, and opioid- agonist drugs are examples of most commonly used intravenous anaesthetics. The first four drugs acts by increasing the central nervous system's (CNS) activity of the inhibitory neurotransmitter GABA. Ketamine inhibits the NMDA receptors' sensitivity to the excitatory neurotransmitter N-methyl-D-aspartate (NMDA), while opioid agonists activate opioid receptors. [5] The most often used induction agent i.e. propofol, or 2,6- diisopropylphenol, due to its advantageous properties, which include quick and fast induction and recovery, a lower risk of post-operative nausea and vomiting, etc. [6,7] The main disadvantages, on the other hand, include a drop in blood pressure, dose-dependent ventilation depression, pain on injection site, thrombophlebitis and sometime pro-epileptogenic. [8–10] Etomidate is carboxylated imidazole include minimal respiratory depression, hemodynamic stability, and CNS protective effects. It is the preferred induction agent for patients with cardiovascular disease because it has least effects on the sympathetic nervous system, the baroreceptor reflex regulatory system, and its ability to promote coronary perfusion even in individuals with mild cardiac ischaemia. [11–14] Nevertheless, some unfavourable side effects include pain at site of injection, thrombophlebitis, and myoclonus. [15, 16] This study was designed to compare intra-operative, post- operative, haemodynamic, respiratory, and neurological response while propofol and etomidate used as induction agent in general anaesthesia.

Study Design: Randomized double blinded controlled trial

Study Site: Department of Anaesthesiology and Critical Care, Nalanda Medical College & Hospital, Patna, Bihar

Study Duration: 2 Years

Source of Data: ASA Grade I and Grade II patients of both sexes between 20 to 65 years undergoing surgery under General Anaesthesia

Ethical Consideration:

The study protocol was approved by the institutional ethics committee of NMCH, Patna and complied with International Conference on Harmonization Guideline for Good Clinical Practice and the Declaration of Helsinki. Informed consent was taken from patients before surgery. Participant Information Sheet (PIS) was provided and explained to patients in their local language. Thereafter, consent was approved by taking their signature or thumb impression on the informed consent form. The data were obtained from the hospital record system after appropriate approval from the concerned authorities.

Sample Size: A total of 60 patients were recruited into the study with 30 patients in each group.

Inclusion criteria:

• Patient of either sex
• Patients of ASA Grade I and II
• Patients of age 20-65 years
• Body weight between 40-78 kg
• Patient undergoing surgery under general anaesthesia

Exclusion criteria:

• Patients with anticipated difficult airway
• Obesity (BMI>35 kg/m2)
• Conditions associated with increased risk of pulmonary aspiration
• Surgery duration greater than 2 hours

30 patients in group P received Inj. Propofol 1% (2 mg/kg of body weight) and 30 patients in group E received Inj. Etomidate (0.3 mg/kg of body weight)

In this randomised double blinded controlled trial, our goal was to find a suitable general anaesthetic induction agent that can have optimal condition for endotracheal intubation and haemodynamic stability. Based on our results, etomidate was found to be a better induction agent in GA. The finding supporting this are discussed below. 43.33% of patients in etomidate group had excellent insertion conditions as comparison to 33.33% in propofol group. 40% of patients in propofol group had poor insertion condition in comparison to only 23.33% in etomidate group.

It is well known that propofol relaxes skeletal muscles in the jaw, but occasionally even a dosage of 3 mg/kg is insufficient to completely regulate the response to LMA placement. To obtund the effects of LMA insertion, it is advisable to add opioids such fentanyl [17]. According to Brown et al., the combination of 2.5 mg per kg of propofol and 1 mcg/kg fentanyl exhibited a positive impact on the responses to LMA implantation [18].

The underlying pharmacological characteristic of etomidate is well characterized, despite the fact that clinical research on the drug are comparatively rare when compared to other drugs like propofol or isoflurane [19]. Etomidate acts as "a positive allosteric modulator of the GABA-A receptor", just like barbiturates as well as propofol do, to generate a hypnotic effect [20]. The primary regulatory receptor in the human nervous system is the GABA-A receptor [21]. Etomidate specifically increases the GABA responsiveness of receptors having the β2 or β3 subunits, whereas other general anaesthetics show minimal selectivity for the various GABA-A receptor variants [23, 22]. It only interacts at the β+/α-domain of the receptor. [24]

"Positive allosteric modulators of the GABA-A receptor" are these anaesthetics. The mechanism and degree of this enhancement varies depending on the anaesthetic’s binding location on the GABA-A receptor as well as the anaesthetic’s dosage [25].

There was significantly more severity of pain on injection site in propofol group as compared to etomidate group.

Propofol injection (POPI) can cause significant discomfort, even though the effects are usually temporary and patients become oblivious to them. In one study, 2.6% of patients remembered experiencing significant pain after the surgery, while 91 percent of patients were unaware of any discomfort at all. [26] An estimated 28–90% of patients experience pain. [Pages 27–29] Research has shown a variety of causes for POPI to date, but little is known about the characteristics of people who may be most impacted.

Numerous variables, such as the injection site, vein size, propofol injection speed, and propofol level, have been proposed to influence the occurrence of POPI. [30] The peripheral intravenous (PIV) location is one element that is frequently mentioned in the literature. Whenever propofol is introduced via the antecubital (AC) vein as opposed to hand IVs, several trials have demonstrated little to no discomfort related to POPI. [29– 32] The length of time exposed to the vein wall, where a slow injection produced greater discomfort than a fast bolus, was another aspect under investigation. [32]

Incidence of apnoea was 76.67% in propofol group as compared to 63.33% in etomidate group. However, the difference between propofol and etomidate group was not statistically significant.

SpO2 of most of the patients in propofol and etomidate group was more than 90%. SpO2 of patients in etomidate group was between 96-98% whereas there was significant decline in SpO2 in propofol group.

The respiratory system is less affected by etomidate than by other anaesthetics like barbiturates or propofol. A brief period of hyperventilation follows the 0.3 mg per kg dosage of etomidate used to induce anaesthesia. A brief episode of apnoea, lasting an average of 20 seconds, was observed throughout multiple patient trials [33, 34]. These apnoea episodes cause a 15% shift in PaCO2 yet have no appreciable impact on PaO2 [33]. The kind of premedication used before etomidate injection appears to have an impact on the incidence of apnoea after anaesthetics induction dosages of etomidate. Etomidate induces a less noticeable reduction of the ventilatory reactions to CO2 than methohexital [34]. When etomidate is administered, there is no discharge of histamine [35, 36].

One of propofol's drawbacks is its significant respiratory depression, which can result in reduced tidal as well as minute volumes as well as a decreased ventilatory reaction to hypoxia [37]. Propofol was found to raise blood CO2 tension, lower the level of hydrogen ion index, and lessen the ventilatory reaction to hypoxia by Blouin et al. [38].

When propofol is infused for sedation following regional anaesthesia in the surgical suite, it has been noted that the dosage of propofol is occasionally raised while the blockage to the airway is cleared using the three-stage airway maneuver if the patient exhibits weak sensitivity to the drug or if the patient moves excessively even after the anaesthesia wears off. [39]

There was significant upsurge in heart rate in propofol group at induction in comparison to etomidate group. There was significant decline in MAP in propofol group at induction in comparison to etomidate group.

Following target-controlled infusion, the impact of propofol on alterations in hemodynamic variables have also been investigated in patients along with healthy volunteers. The most notable hemodynamic impact of propofol is a reduction in sympathetic tone, which causes vasodilation and a drop in peripheral vascular resistance both of which lower MAP. The possibility that postoperative mortality is linked to perioperative hypotension is a major source of worry. [40]

While there is a wealth of descriptive information regarding the relationship among exposure with the cardiovascular risk associated with propofol, just a few mathematical hypotheses have taken into account changes in hemodynamic variables throughout human propofol infusion, while all of them rely on empirical methods that ignore the intricate relationships within the circulatory system. [40]

Etomidate has a number of benefits over other anesthetics, one of which is the preservation of haemodynamic stability. When anesthesia is induced at a dosage of 0.3 mg/kg, it usually does not result in substantial hypotension. This is due to the fact that etomidate maintains autonomic reflexes like the baroreflex therefore does not considerably suppress sympathetic tone.

Etomidate is hypothesized to possess this characteristic due to its agonistic action at α2-adrenoceptors, namely the α2Badrenoreceptor, which is accountable for the peripheral vasoconstriction to low blood pressure. [41]

Numerous studies demonstrate that etomidate anesthetic induction doses in healthy people result in small changes in the heart rate while maintaining key hemodynamic variables like "systemic vascular resistance, cardiac index, pulmonary artery pressure, and central venous pressure". Etomidate is a good anesthetic induction drug for patients with heart disease or hemodynamic instability because of its advantageous cardiovascular profile. The hemodynamic variables are not significantly affected by etomidate anaesthetic induction dosages in individuals suffering from CAD or valvular heart disease. Etomidate has no effect on the oxygen supply-to-demand ratio or myocardial contractility. [41] Incidence of myoclonic movement was slightly greater in etomidate group as compared to propofol group (p>0.05).

Limitation of the Study

Small sample size in the propofol and etomidate group was a limitation due to single cantered design of this study. However, this study may be a foundation stone to affix the appropriate dose and establish universal guidelines in order to find induction agent of choice for LMA to minimize anaesthesia related morbidities.

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