The choice of anesthesia for specific operations can vary greatly based on the country, hospital protocols, and the preferences of both the surgeon and anesthesiologist. For tympanoplasty, general anesthesia or locoregional anesthesia can be employed, with or without sedation [1]. Locoregional anesthesia has several advantages, like patient cooperation during facial nerve monitoring, intraoperative hearing testing, faster recovery, and early discharge. In addition to anesthesia, another requirement during the surgery is a bloodless surgical field. Local infiltration with a local anesthetic and adrenaline combination is most frequently used to provide an optimum surgical field. However, as adrenaline is absorbed into the body, it can cause several harmful side effects. Therefore, a substitute of adrenaline is required to provide similar conditions but with minimal side effects.

Dexmedetomidine (DEX) has been approved to be used as an adjuvant through the intravenous route. Various previous studies have shown multiple benefits of DEX as an intravenous adjuvant in dose, ranging from 0.5 µg/kg to 3 µg/kg [2-4]. Other routes of DEX administration are also being explored. Several research investigations have been conducted to compare the effectiveness of adrenaline and DEX as adjuvants with local anesthetics for infiltration in various surgical procedures [5,6]. Ouchi et al. [7] found that DEX enhances the local anesthetic action of lidocaine in a dose-dependent manner in a rat TF model. Other beneficial dose-dependent effects of DEX are sedation, analgesia, sympatholytic action, and reduced anxiety without respiratory depression or wide hemodynamic fluctuation.

Local use of DEX as an adjuvant can reduce its systemic side effects, such as dry mouth, bradycardia and hypotension risk, and deep sedation. Research conducted on both animals and humans has put forth several hypotheses to elucidate its localized impact, although the precise mechanism remains uncertain. In addition, its effect on the 2-beta receptor in smooth muscle cells of the peripheral blood vessels might cause the capillaries to constrict, resulting in a decrease in blood loss and absorption of local anesthetic. Several trials have administered it locally together with LA at varying doses (ranging from 0.5 µg/kg to 5 µg/kg) for a variety of surgical procedures [8-10].

There is a gap in the literature regarding a safe dose of DEX for optimum effect when used as an adjuvant to a local anesthetic to be used for tympanoplasty. Our hypothesis was that administering a higher dose of DEX would result in both a localized effect and systemic benefits. Therefore, we conducted this study to compare two standard doses of DEX in order to achieve a bloodless surgical field while minimizing adverse effects. The primary objective of this study was to compare the intraoperative bleeding at the surgical site with the use of 0.5 µg/kg and 1 µg/kg DEX with 2% lidocaine for local infiltration. The secondary objectives were time of first analgesia requirement, degree of sedation, surgeons’ satisfaction, and intraoperative hemodynamics.

A prospective, randomized, controlled, triple-blinded study was designed in a tertiary care center. This trial was approved by the institutional ethics committee (1064/1EC/IGIMS/2023) and registered at the Clinical Trials Registry-India, www.ctri.nic.in (CTRI/2023/09/057450, September 11, 2023). The study enrolled patients between October 2023 and January 2024, adhering to the principles of the Declaration of Helsinki (2013) and good clinical practice.

The study enrolled patients between the ages of 18 and 65, with physical statuses I to II according to the American Society of Anesthesiologists, scheduled for tympanoplasty under local infiltrative block and under monitored anesthesia care. Exclusion criteria were patient refusal, severe cardiopulmonary diseases, allergy to local anesthetics, inability to communicate and cooperate, or infection at the surgical site.

After preoperative screening for eligibility, written informed consent was obtained. According to computer-generated codes, using the permuted block randomization method with a block size of eight, patients were randomized to two equal groups by sequentially numbered, sealed opaque envelopes, which were opened after recording of baseline parameters. Patients in DEX 0.5 group received 10 ml of 2% lignocaine with 0.5 µg/kg DEX, and in DEX 1.0 group, patients received 10 ml of 2% lignocaine with 1 µg/kg DEX. The dosage of DEX was determined based on the patient's body weight and estimated using the Broca method if the patient weighed more than 100 kg. The patient, the surgeon administering the local anesthetic, and the anesthesiologist assessing the patient intraoperatively were blinded to group allocation. An anesthesia resident not involved in the study prepared the drug for infiltration in a 10 ml syringe.

After securing 18-gauge peripheral venous access and applying American Society of Anesthesiologists standard monitors (pulse oximetry, noninvasive blood pressure, electrocardiogram, temperature), the baseline parameters were recorded. Then, patients were handed over to the surgeon for local infiltration with the drug prepared according to the group randomization. The technique of infiltration was standardized by administering 2 ml of fluid at each of the five points around the auricle using 26-gauge needles (Fig. 1) [11]. All hemodynamic parameters were recorded at the end of infiltration, and the timer was started on the anesthesia machine. The surgeons were allowed to give the surgical incision after 15 min of drug infiltration. Fentanyl 0.5 µg/kg IV was administered intraoperatively as a rescue medication in response to patient movement or complaints of pain with a visual analogue scale (VAS > 3). The medication might be repeated as necessary. The anesthesia procedure was converted to general anesthesia at any timepoint intraoperatively if the sedation score became ≥ 5. Following the completion of surgery, patients were sent to the recovery room for two h in order to monitor their vital signs and detect any potential side effects. In order to manage pain after surgery during the first 24 h, patients were administered intravenous paracetamol (1 gram) if their VAS score exceeded 3.

A total of one hundred and ten patients were enrolled in the current study, of which ninety-eight were randomized in two groups of forty-nine each. All the patients received the study treatment according to the allocated group. Four patients in each group were not included in the final analysis due to conversion to general anesthesia or abandonment of surgery, as can be seen in the CONSORT diagram (Fig. 2).

In this trial, we selected two different doses of DEX as an adjuvant for infiltration for nerve block. The study found that using DEX at a dose of 1 µg/kg, in addition to 2% lignocaine, for infiltration anesthesia in tympanoplasty surgery was more effective than using a dose of 0.5 µg/kg DEX in achieving a bloodless surgical field (with a bleeding score of 1.43 ± 0.661 compared to 3.21 ± 0.727). The higher dose of DEX resulted in significantly improved intraoperative sedation scores and surgeon satisfaction without causing any hemodynamic instability. The incidence of hypotension and bradycardia was low in both groups, and it was not clinically significant as no rescue medication was required. The additional advantage, apart from creating a bloodless field, was achieved due to the better sympatholytic effect of the higher dose used for local infiltration.

An optimal anesthetic method for tympanoplasty should maximize the visibility of the surgical area while avoiding significant low blood pressure and enabling real-time monitoring of facial nerve activity. Additionally, it should minimize the risk of severe coughing during recovery and postoperative nausea and vomiting. Historically, adrenaline has been employed in conjunction with local anesthetics to reduce blood loss and prolong the analgesic effects by inducing local vasoconstriction. However, it lacks any inherent sedative or analgesic effects. Moreover, it can be associated with serious side effects like anxiety, dizziness, palpitations, sweating, shortness of breath, flushing, chest pain, tremors, and nausea [12]. Furthermore, it is not recommended for individuals with cardiac disorders, uncontrolled hypertension, and hyperthyroidism. As a substitute or supplement to adrenaline, α2 agonists like clonidine and DEX have been explored in microsurgeries [13-15]. A systemic review and meta-analysis was done by Tirupathi et al. [16] on the use of clonidine versus adrenaline as an adjunct to lignocaine for nerve block for dental surgeries. The majority of studies included in the review reported a significant drop in mean heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure during the intraoperative period when clonidine was administered as a vasoconstrictor. Conflicting results were however reported for the duration of anesthesia, where clonidine increased the duration on subjective assessment (numbness) in comparison to epinephrine, while epinephrine increased the duration when measured objectively (pin prick). This might be due to the difference in the number of studies that evaluated subjective and objective parameters. The results of this meta-analysis pointed towards the use of clonidine with lignocaine for nerve blocks in hypertensive patients undergoing dental surgeries.

The efficacy of intravenous DEX in reducing surgical hemorrhage in microscopic procedures has been evaluated satisfactorily. The results were encouraging with clear surgical field, adequate sedation, and duration of analgesia. Nalawade et al. [4] discovered that the combination of lignocaine and DEX provided superior surgical conditions, a quicker onset of anesthesia, extended pain relief, and lower hemodynamic values in comparison to the combination of lignocaine and adrenaline [2]. The analgesic and vasoconstrictor effects of DEX have been investigated in similar procedures by delivering it through various routes of administration. Motlagh et al. [17] used different intravenous doses of DEX and observed improved surgical field with higher doses, but also increased chances of bradycardia. But, in our trial, we found better visibility of the surgical field without clinically significant bradycardia. The possible reason could be the local infiltration as the route of administration, as it generates a low steady plasma concentration. We compared two distinct doses of DEX, hypothesizing that the lower dose could produce local effects, whereas systemic benefits might require a higher dose to build up drug plasma concentration. Both effects are critical for achieving favorable results for the surgeon and the patient. No study has been found that measures the plasma level achieved after local infiltration of DEX. Wu et al. [18] conducted a comparison of the effects of different routes of DEX and found that the intravenous route yielded the most favorable surgical field compared to the nasal or oral route. The peak plasma concentration in individuals administered with intravenous and nasal methods was attained at 13.2 min and 70.3 min, respectively. However, the oral route did not result in the attainment of the peak plasma concentration [18].

The other potential advantage of DEX observed in our trial was controlled hypotension without bradycardia, thereby decreasing bleeding and further increasing the efficacy of DEX. It produces hypotension at low plasma concentrations and hypertension with bradycardia at higher plasma concentrations. The infiltration route creates possibly a low plasma concentration, thus direct α2 receptor activation and thereby reflex baroreceptor reflex are avoided. No respiratory depression was observed, which becomes clinically more significant in tympanoplasty, where the patient's face and upper body are under drape.

The typical discomforts experienced by patients undergoing tympanoplasty include surgical noise, anxiety, vertigo, lower back pain, claustrophobia, and ear pain. DEX induces a sleep-wake cycle that closely resembles the natural physiological pattern while also producing sedation that can be easily interrupted. Analgesic action of DEX has central and local perineural mechanisms with prolonged hyperpolarization of sensory C fibers and motor A fibers. Additionally, our findings indicate that administering a higher dose of DEX resulted in a significantly prolonged period of pain relief, improved sedation scores, and reduced patient movement during surgery. The aforementioned attributes of DEX resulted in increased patient satisfaction.

Compared to adrenaline when DEX was used as an adjuvant, the additional benefit of procedural sedation produced a smooth and calm patient, as observed by our sedation score. Both the patient and the surgeon expressed a high level of satisfaction with the use of DEX, which effectively provided comprehensive anesthesia by infiltration route.

Our technique of local infiltration was standardized and robust, thereby reducing the incidence of operator bias. We administered the recommended higher dosage of DEX in the infiltration block without observing any adverse reactions.

Unfortunately, we were unable to quantify the plasma levels of DEX at various time intervals due to its unavailability at our institution. While we have established a uniform approach for the local infiltration technique, it is important to note that operator bias cannot be completely eradicated.