TITLE: A prospective randomised clinical study to compare the Effects of Esmolol and Dexmedetomidine and their effectiveness to provide quality surgical field during Functional Endoscopic Sinus Surgeries

BACKGROUND & RATIONALE : Functional endoscopic sinus surgery (FESS) is a commonly performed procedure in otorhinolaryngology and involves the manipulation of the nasal and paranasal sinuses to re- establish sinus ventilation and restore its function. Indications of FESS are chronic sinusitis refractory to medical treatment, recurrent sinusitis, nasal polyposis, antrochoanal polyps, sinus mucoceles, excision of selected tumours, cerebrospinal fluid leak closure, orbital decompression, optic nerve compression, dacryocystorhinostomy, choanal atresia repair, foreign body removal, epistaxis control etc,

Impaired visibility due to excessive bleeding has been a major hurdle that has been reported for FESS under general anaesthesia. Intraoperative bleeding may be reduced effectively by induced systemic hypotension. There are several important advantages of using the induced hypotensive anaesthetic technique during FESS like reduction in blood loss, hence reduction in blood transfusion rate, improvement in the surgical field, and reduction of the duration of surgery in hypotensive anaesthesia, the patients mean arterial pressure (MAP) is reduced by 30% or MAP was kept at 60-70mm Hg.

Deliberate hypotension was first introduced in 1917 by Harvey Cushing in order to provide a bloodless field for neurosurgery. In 1946, the concept of induced hypotension using arteriotomy to produce a bloodless field was introduced by Gardner. In hypotensive anaesthesia, the patient’s baseline mean arterial pressure (MAP) is reduced by 30% or MAP is kept at 60-70 mmHg. The finding suggested that there is an increased risk of postoperative acute kidney injury when the intraoperative MBP is <60 mmHg for over 20min and <55 mmHg for more than 10 min.

The principle of induced hypotension is MAP = CO X SVR. MAP can be manipulated by reducing SVR or CO or both.CO can be reduced by decreasing venous return, heart rate, cardiac contractility or combination while SVR can be reduced by peripheral vasodilation.

An ideal hypotensive agent should be easy to administer, should have a short onset time, should have effects that disappear quickly when the administration is discontinued, should be rapidly eliminated without toxic metabolites, should have a negligible effect on vital organs and should have predictable and dose-dependent effects.Volatile anaesthetics, sympatholytics, beta-adrenoreceptor antagonists, calcium channel blockers, opioids, and direct-acting vasodilators have been used to achieve controlled hypotension.

The aim of induced hypotension is to lower MAP while maintaining adequate perfusion to all vital organs. Thus, preoperative fluid status must be assessed and corrected. At the same time maintenance volume need to be infused. Blood loss must be replaced with an equal amount of colloid or three to four times the amount of crystalloid.

Contraindications for hypotensive anaesthesia are patient-related and anaesthesia related. Anaesthesia related are lack of experience and inability to monitor patients properly. Patient- related contraindications are cardiac disease, renal disease, diabetes, history of hypertension, ischemic cerebrovascular disease, anaemia, haemoglobinopathies, polycythaemia, and respiratory insufficiency.

AIM: To compare the effects of esmolol and dexmedetomidine and their effectiveness to provide quality surgical field during Functional Endoscopic Sinus Surgeries(FESS).

OBJECTIVES:

Primary Objective:

1.     To assess and compare the haemodynamic parameters like heart rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure from baseline at different time intervals in both groups.

Secondary Objective:

1.     To assess and compare the quality of the intra-operative surgical field by using the average categorical scale in both groups.

2.     To assess and compare emergence time, sedation score, VRS scale score in the post-operative field and time to first rescue analgesic after surgery.

3.     To find out and compare the proportion of cases with complications.

HYPOTHESIS

Null hypothesis (H0)-There is no significant difference between the efficacy of esmolol vs dexmedetomidine on hemodynamic variables of surgical patients.

The alternate hypothesis (H1)-There is a significant difference between the efficacy of esmolol vs dexmedetomidine on hemodynamic variables of surgical patients.

METHODOLOGY

STUDY LOCATION:

The study will be conducted in the Department of Anaesthesiology, JLN Medical college and the associated group of hospitals, Ajmer with due permission from the institutional ethics committee and written informed consent.

STUDY DESIGN:

Hospital-based prospective, double-blind, randomised interventional study.

STUDY DURATION:

1year and 6 months (including data collection and analysis).

STATISTICAL ANALYSIS:

The sample size of 30 in each group at 95% confidence & 80% power would be adequate to verify the expected difference of 8.4%(+-10.6%)in a change in mean systolic blood pressure from baseline to 30 minutes post-induction period as per the seed article. This sample size is adequate to cover all other study variables also.

Standard qualitative and quantitative tests will be used to compare the data ( e.g. paired or unpaired student t-test, ANOVA, Chi-Square).

RANDOMIZATION:

60 eligible cases will be allocated into two study groups using the sealed envelope method.

BLINDING:

This trial is so planned that neither doctor nor the patient will be aware of the groups and drugs used.

INCLUSION CRITERIA:

1.   Either sex

2.  Age group 18-65yrs

3.   Body weight 40-70kg

4.  ASAGrade I&II

5.   Scheduled for surgery under general Anaesthesia

EXCLUSION CRITERIA:

1.     Patients not willing to participate in the study Uncooperative patients

2.   Patients with a history of drug allergy

3.   Patients with pre-existing, Asthma, Renal or Hepatic dysfunction

4.   Pregnancy/Lactation

5.   Morbid obese patient

ALLOCATION OF GROUPS: Patients will be randomly allocated to 2 groups (30 patients in each group).

Group A (Esmolol Group) - Patients will receive Inj. esmolol bolus 1mg/kg over 1 minute before induction followed by an infusion of 1mg/kg/hr through an infusion pump. Group B (Dexmedetomidine Group)– Patients will receive a bolus dose of 1mcg/kg dexmedetomidine diluted with 19ml Normal Saline and taken in 20ml syringe and given over 10 min intravenously by syringe pump before Induction followed by 100mcg dexmedetomidine taken in 19ml Normal Saline inside a 20ml syringe (5mcg/ml) and given as 0.5mcg/kg/hr i.v. infusion intraoperatively.

PRE-ANAESTHETIC CHECK-UP

All patients will be visited 1 day prior to surgery and explained about the anaesthetic technique and perioperative course and VNRS (Verbal Numeric Rating score). Each patient will have a pre-anaesthetic checkup which includes:

1.  Any significant present/past medical/surgical history

2.   Physical examination

3.  Vital parameters like B.P/Pulse/Temperature/Respiratory rate

4.   Routine investigations-Hb, TLC, DLC, Bleeding time, Clotting time, Fasting blood sugar, S. urea and creatinine, SGOT, SGPT, Chest X-Ray, ECG, Platelet count and INR.

5.  Written and informed consent will be obtained for the performance of general anaesthesia after a complete explanation of the study protocol and the procedure

PROCEDURE:On arrival in the operation theatre, fasting status, written informed consent and PAC will be checked. Routine noninvasive monitors attached and Systolic blood pressure (SBP), Diastolic blood pressure (DBP), Mean arterial pressure(MAP), and SpO2 will be noted.

ECG & ETCO2 will be attached to the patient. An intravenous line will be secured, and i.v. fluid R.L. will be started at 5ml/kg/hour. patients who are assigned Group A (Esmolol Group) - Patients will receive Inj. Esmolol bolus 1mg/kg over 1 minute, while Group B (Dexmedetomidine Group)– Patients will receive bolus dose 1mcg/kg dexmedetomidine diluted with 19ml Normal Saline and taken in 20ml syringe and given over 10 min intravenously by syringe pump respectively. Inj glycopyrrolate 0.2 mg intravenously (i.v.) will be given. After preoxygenation with 100% O 2 for 3 min, anaesthesia will be induced with propofol (1%) 1.5-2.5 mg/kg i.v. till loss of response to verbal commands.Endotracheal intubation with an adequate-sized, cuffed endotracheal tube will be facilitated by neuromuscular blocker succinylcholine 1.5 mg/kg i.v. Anaesthesia will be maintained with oxygen and nitrous in a ratio of 1:1 along with sevoflurane (0.8-2%) on controlled mechanical ventilation. Group A (Esmolol Group) will receive an infusion of 1mg/kg/hr esmolol through an infusion pump while Group B (Dexmedetomidine Group) will receive 100mcg dexmedetomidine taken in 19ml Normal Saline inside a 20ml syringe (5mcg/ml) and given as 0.5mcg/kg/hr i.v. infusion. Vital parameters, including HR, blood pressure, electrocardiogram, temperature, and end-tidal CO 2 and O 2 saturation, will be monitored throughout the procedure.