Effects of Remifentanil and Dexmedetomidine with Propofol on Laryngeal Mask Airway Insertion, Hemodynamic Stability, and Pharyngolaryngeal Morbidity: A Prospective Study of 80 Patients

Introduction

Airway management is one of the basic topics in anesthesia practice. Standard methods used with this aim are endotracheal intubation and face masks [1]. In 1981, Dr. A. Brain designed the laryngeal mask airway (LMA) to avoid common problems with airway management [1,2]. Although it initially began to be used as an alternative to face masks, with new modifications added, it is currently used when endotracheal tubes are needed [1,2].

As LMA insertion is performed blind without a laryngoscope, it can be completed without muscle relaxants with sufficient anesthesia depth provided at lower doses than for endotracheal intubation [3,4]. Proper insertion and accurate placement of LMA is possible by providing anesthesia depth at levels that allow sufficient chin relaxation and suppress upper airway reflexes [5]. Propofol was found to be superior to other induction agents in terms of suppressing upper airway reflexes and success of LMA insertion and is the most frequently chosen hypnotic agent with this aim [4,6,7]. However, when used alone at the recommended induction doses, sufficient conditions for LMA insertion cannot be provided [7–9]. For optimal LMA insertion conditions, a high bolus dose or target plasma concentration that can result in severe cardiorespiratory depression are reported to be needed [10]. Remifentanil is an ultra-short-effect, selective μ-opioid receptor agonist, with effect independent of duration of drug administration [8]. In previous reports, administration of remifentanil before induction with propofol was reported to clearly increase perfect and/or acceptable LMA insertion conditions and success of intubation without muscle relaxants compared to administration of propofol alone or with other opioids [2,5,8,11–13]. This is an important consideration for the appropriate selection of induction agents, especially in cases where non-depolarizing muscle relaxants should be avoided (such as in patients with myopathies or those at risk for allergies) or where depolarizing muscle relaxants are contraindicated (such as in conditions like malignant hyperthermia, hyperkalemia, burns, plasma cholinesterase deficiency, and penetrating eye injuries) [13]. However, the use of a depolarizing neuromuscular blocker agent, such as succinylcholine, during induction, even at low doses, increases the risk of malignant hyperthermia, arrhythmia, anaphylaxis, and severe postoperative myalgia. Furthermore, priming with a neuromuscular blocking agent can lead to problems such as double vision, hypoventilation, and aspiration, along with a greater decline in desaturation and pulmonary function, particularly in elderly patients [13,14].

Dexmedetomidine is a strong and very selective a2-adrenoceptor agonist for a2 receptors with 1620: 1 a2: a1 ratio. It has sedative, anxiolytic, sympatholytic, and analgesic effects and suppresses respiratory functions at minimal levels [15]. Several reports have shown that dexmedetomidine is a beneficial adjuvant that reduces airway reflexes and the hemodynamic response to stimuli such as LMA and endotracheal intubation without increasing apnea duration [14–22]. However, our literature search found no study comparing the effect of the combination of remifentanil, frequently chosen in outpatient surgery especially due to similar pharmacokinetic features, and dexmedetomidine with propofol on LMA insertion conditions without the use of muscle relaxants. Therefore, this retrospective study included 80 patients aged 18–65 years undergoing elective surgery requiring laryngeal mask airway insertion, and aimed to compare outcomes following propofol-dexmedetomidine and propofol-remifentanil in terms of LMA insertion conditions, hemodynamic response, and pharyngolaryngeal morbidity, with surgeries lasting less than 2 hours and not requiring intubation (Figure 1).

Material and Methods

STUDY DESIGN:

This prospective, randomized, controlled trial with a parallel-group design was conducted in accordance with the Declaration of Helsinki and was approved by the Okmeydani Education and Research Hospital Medication Research Local Ethics Committee (decision number: 134). All patients provided written informed consent prior to participation in the study, acknowledging their understanding of the study’s purpose, procedures, and potential risks. This study was a prospective, randomized, controlled trial with a parallel-group design. Randomization was performed using a closed envelope method to ensure the integrity of group allocation. The primary outcomes were LMA insertion conditions, time to eyelash reflex loss, and time to successful LMA insertion, while the secondary outcomes were hemodynamic response, apnea duration, pharyngolaryngeal morbidity, and incidence of complications. The trial is registered under the Australian New Zealand Clinical Trials Registry (ANZCTR) with the registration number ACTRN12625000184471.

PARTICIPANTS:

The study included 80 patients in Groups I–II according to the ASA physiological classification, age 18–65 years, undergoing elective surgery, without requiring muscle relaxants, with operation duration not over 2 hours, and with indications for LMA insertion (Figure 1). We excluded patients with any neck and upper respiratory tract pathology, history or possibility of difficult airway (Mallampati class 3–4, sternomental distance less than 12 cm, thyromental distance less than 6 cm, head extension less than 90 degrees, mouth opening less than 1.5 cm), with morbid obesity, history of heart failure, hypertension, pulmonary disease, history of allergy to the study drugs, history of alcohol and substance dependence, history of chronic sedative and opioid analgesic use, throat pain, dysphagia, and dysphonia.

INTERVENTIONS AND DATA COLLECTION:

Before anesthesia, patients taken to the operating room had standard monitoring performed: heart rate (HR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), electrocardiography (ECG-derivation II), and peripheral oxygen saturation (SpO2). Anesthesia depth was monitored with bispectral index monitoring using BIS-Vista™ (Aspect Medikal Sistemler; Newton, MA, USA) [2]. Patients had venous access in the back of the hand with a 20 G cannula and were administered 7 ml·kg−1 saline infusion before induction [13]. Patients were randomly assigned to 2 groups (Group D and Group R, n=40 in each group) with the closed envelope method and received 1 μg·kg−1 dexmedetomidine or 2 μg·kg−1 remifentanil. Coded test syringes were prepared with a total of 50 mL to 20 mL volume with 0.9% saline by an independent anesthesia expert. The anesthesiologist inserting the LMA and monitoring parameters was blinded to the drug doses, so all syringes were injected by an assistant behind a screen. Preparation and administration of drugs and insertion of LMA and monitoring of parameters were performed by different anesthesiologists. In this way, the anesthesiologist inserting the LMA, monitoring the patient response to LMA, and recording the parameters was blind to the drugs administered [13]. About 3 minutes before induction, all patients were given preoxygenation with 6 L/min oxygen through a face mask [3,15] and 0.3 mg·kg−1 IV midazolam (Dormicum® ampoule, Roche müstehzarları Sanayi, İstanbul) was administered [6].

Patients in Group D were given 1 μg·kg−1 dexmedetomidine in a 50 mL injector completed to 50 mL with 0.9% NaCl (Precedex®, 100 μg·mL−1, Hospira, USA) infused over 10 minutes with an infusion pump (Braun Infusomat®; Braun Melsungen Ko, Germany). Patients in Group R were given the same volume of 0.9% NaCl infusion. In the last 60 seconds of the 50 mL infusion, patients in group R were given 2 μg·kg−1 remifentanil after completion to 20 ml with 0.9% NaCl with an infusion pump for 60 s (Braun Infusomat®; Braun Melsungen Ko, Germany). Patients in Group D had the same volume of 0.9% NaCl infused. Thirty seconds after the 20 mL infusion, 2.5 mg·kg−1 propofol was administered over 30 seconds for anesthesia induction [15–18]. In the perioperative period, if hypotension occurred (<30% reduction in MAP compared to basal values), 6 mg ephedrine (Efedrin, Haver, İstanbul, Türkiye) was administered. Bradycardia was defined as HR less than 50 beats/min; if it occurred, 0.5 mg IV atropine (atropine sulphate, Haver, İstanbul, Türkiye) was administered [13].

MONITORING AND OUTCOMES MEASUREMENTS:

With eyelash reflex checks after induction, patients were ventilated with 100% O2 using a face mask [12]. The duration to loss of eyelash reflex was determined as the time from the beginning of administration of the induction agent until the eyelash reflex was lost [2]. At 90 seconds after propofol administration [3], once the BIS value dropped below 40 [2] and sufficient jaw relaxation was achieved, the size of the LMA was determined according to the patient’s body weight as recommended in the manufacturer’s instruction manual. The oropharyngeal side of the LMA was lubricated with a water-soluble gel, and with the cuffs fully deflated, it was inserted using the standard method described by Brain by a single researcher who had more than 3 years of experience [6,19]. After inserting the laryngeal mask, cuff pressure monitoring (cuff pressure manometer, Rüsch, Germany) was performed to standardize results on postoperative pharyngeal morbidity. The laryngeal mask cuff was inflated until the cuff pressure reached 60 cmH2O and this value was kept fixed (cuff pressure manometer, Rüsch, Germany) during the operation [14,20,21].

The duration until successful insertion (duration from opening of mouth to first successful ventilation) was recorded [22]. Criteria for successful insertion of the laryngeal mask were observing square waveforms on the capnogram, easy ventilation with a respiratory balloon, ability to see chest movements, and no air leak with 20 cmH2O positive-pressure ventilation [22,23]. Anesthesia maintenance ensured BIS values were between 40 and 60 [2] and was provided with 1.5–2% sevoflurane concentration within a 40% O2/60% N2O mixture [16]. If sufficient induction could not be provided for patients, if no movement was observed during the first attempt, and after 1 mg/kg propofol additional dose if necessary to keep BIS values below 40, LMA insertion was attempted a second time [2,24]. The number of attempts was recorded; however, LMA insertion conditions were only assessed during the first attempt [25]. In the event of failure after 2 attempts at placement – defined as inability to achieve adequate ventilation, presence of an audible air leak that could not be resolved by positional adjustments, hypercarbia (end-tidal CO2 >45), or hypoxemia (SpO2 falling below 90% at any point during the study, or complete laryngospasm) – intubation was performed, and the patients were excluded from the study [2,19,26–28]. When assessing LMA insertion conditions, a 6-variable scale used in previous studies and including chin opening, ease of insertion, swallowing, coughing/retching, laryngospasm, and movement of the patient was used. The tolerance of patients to LMA insertion was assessed. LMA insertion conditions were evaluated within 2 groups: perfect means all criteria were perfect, good means all criteria were a mix of moderate and perfect, and poor means 1 or more criteria were poor [5] (Table 1).

In both groups, SAP, DAP, MAP, HR, BIS and SpO2 values were recorded at baseline, immediately before LMA insertion, and at 1, 2, 3, 4, and 5 minutes after insertion, and apnea duration (duration from last spontaneous respiration before induction to start of first spontaneous respiration) was recorded [3]. Five minutes before the end of the operation, 100% O2 was administered. Before removing the LMA, the intracuff pressure was measured again and recorded. In the presence of sufficient ventilation, the LMA was removed and the duration of LMA use was recorded (duration between insertion and removal) [21]. After removing the laryngeal mask, the presence of blood was assessed as 1: no blood seen, 2: trace amounts, and 3: significant amount of blood [27]. Waking patients were sent to the recovery unit with 100% oxygen. To determine the frequency and severity of pharyngolaryngeal complications, a single researcher, blind to group assignment and not involved in the anesthesia process, evaluated all patients on discharge from the recovery unit for throat pain (constant pain, independent of swallowing) and dysphagia (difficulty with swallowing provoked by drinking). In the postoperative period, patients were questioned about the presence/absence of these symptoms. Throat pain was assessed as follows: 0 points were no pain, 1 point for mild throat pain, 2 points for moderate throat pain, and 3 points for severe throat pain [21]. Perioperative hypotension (<30% decrease in MAP compared to baseline value) was treated by administering 6 mg of ephedrine (Ephedrine, Haver, Istanbul, Turkey). Bradycardia was defined as HR below 50 beats/min and was treated with 0.5 mg IV atropine (Atropine Sulphate, Haver, Istanbul, Turkey) [13].

STATISTICAL ANALYSIS:

Data were evaluated using the IBM SPSS Statistics 26.0 (IBM Corp., Armonk, New York, USA) statistical package program. Descriptive statistics are presented with n,% for categorical variables, and the normality assumption of the data for continuous variables was examined with mean, standard deviation or median, and interquartile range (IQR) values. The Shapiro-Wilk test was used to examine the distribution assumptions of continuous variables according to groups.

The homogeneity of variances of continuous variables according to groups was evaluated with the Levene test. The independent-sample t test or Mann-Whitney U test was used to evaluate the means or distributions of 2 independent groups of continuous measurements. Pearson chi-square test, Fisher exact test, and Yates continuity correction test were used to examine the relationship between categorical variables. Variance analysis was used in repeated measurements in the evaluation of heart rate and hemodynamic data according to D and R groups at 5 different times before, during, and after baseline. The Bonferroni multiple comparison test was used for comparisons between times. p<0.05 was considered statistically significant.

POWER ANALYSIS:

Post hoc power analysis was conducted using G Power 3.1.9.6 software. When the distributions for excellent LMA insertion conditions in the excellent groups were set to 0.568 and 0.973, respectively, and with a Type I error of 0.05 and a two-tailed hypothesis, the test power was calculated to be 82.62%.

Results

DEMOGRAPHIC AND BASELINE CHARACTERISTICS:

The groups were comparable in terms of demographic characteristics, including age, sex, and weight. Group D had an average age of 35.36±9.02 years, while Group R’s average age was 36.38±8.20 years (p=0.615). Sex distribution was similar in both groups, with no significant differences (Group D: 48.6% female, 51.4% male; Group R: 45.9% female, 54.1% male). Body weight did not differ significantly between groups (Group D: 75.36±13.88 kg, Group R: 70.57±10.73 kg, p=0.163) (Table 2).

Discussion

Our study results demonstrated that, in healthy, premedicated patients with appropriate airway anatomy, the administration of 2 μg·kg−1 remifentanil before induction with propofol, compared to a bolus of 1 μg·kg−1dexmedetomidine, led to significantly greater suppression of MAP without increasing the risk of bradycardia or hypotension. It also resulted in a longer apnea duration, shorter LMA placement time, and shorter eyelash reflex loss duration, along with a higher rate of excellent LMA placement conditions (97.3% vs 56.8%, respectively) and similar rates of acceptable LMA placement ease (100% vs 97.3%, respectively). According to our literature search, this is the first study comparing the effects of dexmedetomidine versus remifentanil administered before induction with propofol on LMA insertion conditions, hemodynamic response, and pharyngolaryngeal morbidity.

Propofol is known to make LMA insertion easier by reducing upper respiratory tract muscle tone and suppressing pharyngolaryngeal reflexes [4,7]. However, in several studies, induction with propofol as a single agent in patients without premedication has been reported to result in reflex responses such as swallowing, gagging, coughing, laryngospasm, movement responses, and inadequate jaw relaxation, at rates ranging from 26% to 80% [7,9,29]. This means that the use of propofol alone does not always guarantee successful insertion of LMA. For this reason, several agents, such as low-dose mivacurium [30], isoflurane [7], intravenous lidocaine [9], intravenous midazolam [29], fentanyl [11], alfentanil [11,29], and remifentanil [2,5,8,11], have been used with propofol as adjuvants to improve LMA insertion conditions and reduce dose requirements.

Remifentanil is successfully used with propofol for tracheal intubation without muscle relaxants and for LMA insertion [5,31]. Bouvet et al administered remifentanil along with 2.5 mg·kg−1 propofol to healthy female patients who received premedication, and reported that the remifentanil dose required to achieve perfect muscle relaxant-free intubation conditions for 95% of patients with acceptable hemodynamic tolerance was 4 μg·kg−1. They also found that the dose required to achieve perfect LMA insertion conditions for 95% of patients was 1.32 μg·kg−1. This dose for LMA insertion is approximately one-third of the dose required for tracheal intubation. However, these 2 dose-response studies only included female patients [5,31]. Joe et al [32] noted that the effect-site concentration (Ce) of remifentanil required to facilitate successful LMA placement following propofol induction was higher in men than in women. Therefore, it was recommended to consider sex for appropriate dosing when using remifentanil for LMA insertion. As a result, in our study, by noting that the remifentanil dose required for LMA insertion should not be less than one-third of the dose needed to obtain 95% rates of perfect muscle relaxant-free intubation when administered with 2.5 mg·kg−1 propofol, we determined the dose as half of this value.

Dexmedetomidine produces a typical biphasic hemodynamic response due to hypotension at low plasma concentrations and hypertension at high plasma concentrations. Rapid and/or high-dose dexmedetomidine administration causes a hypertensive response accompanied by bradycardia with hypertension linked to the baroceptor reflex response with α2-reseptor activation in vascular smooth muscle. Several minutes later, vasoconstriction lessens, linked to the reduction in plasma concentration. Simultaneous to vasodilatation, activation of α2 adrenoreceptors in vascular endothelial cells and presynaptic activation of α2 adrenoreceptors in the central nervous system results in a hypotensive phase accompanied by bradycardia and hypotension with increasing cardiovagal activity against the reduction in sympathetic activity [15,16,21,33]. Compared to basal values, a mean fall of 13–27% is observed in MAP [15]. Slow infusion of the drug over 10 minutes or more results in long-term stabilization with values a little below initial values for heart rate and blood pressure [16]. Additionally, administration of dexmedetomidine with a preoperative single dose in 10 minutes of 0.5–1 μg·kg−1 without continuous infusion was reported to effectively suppress the increase in MAP and HR associated with LMA or intubation, along with improving LMA insertion conditions [15,16,20,21]. As a result, in our study we administered dexmedetomidine as 1 μg·kg−1 IV infusion in 10 minutes before induction.

As opioids suppress the central cough reflex and airway irritability in a dose-associated manner, they are the most frequently used adjuvant agents [34]. Remifentanil is a new, ultra-short-effect, selective μ-opioid receptor agonist. The ester bond makes this sensitive to hydrolysis by blood and non-specific tissue esterases; therefore, it has a short terminal half-life duration of <10 minutes independent of dose and administration duration. When administered with propofol, it is reported to be superior to fentanyl [11,35] and alfentanil [11] administration due to ensuring LMA insertion success of up to 100% and perfect or acceptable LMA insertion conditions with more hemodynamic depression, along with more rapid induction and shorter apnea duration [11,14,29]. Dexmedetomidine is a frequently used selective and strong a2-adrenoceptor agonist with anxiolytic, sedative analgesic, and sympatholytic features [15]. IV doses of 0.5–2 mcg·kg−1 have sedative effects, as well as anesthetic and analgesic effects, and it was shown to reduce the induction and maintenance dose requirements for propofol [3,18,19,21]. In previous reports, administration of 1 ug·kg−1 dexmedetomidine before induction with 2–2.5 mg·kg−1 propofol was reported to have lower cough, swallowing, and movement response, greater full chin opening, less respiratory depression, and increased bradycardia risk, and provided comparable levels of perfect and/or acceptable LMA insertion conditions compared to 1 mg·kg−1 fentanyl administration [3,16–18,22]. As a result, in our study, when using propofol, we compared the effect of administration of dexmedetomidine with remifentanil on LMA insertion conditions, providing rapid recovery even after long-duration outpatient procedures due to its more potent and ultra-short effect duration compared to fentanyl. We found that remifentanil and dexmedetomidine pre-administration resulted in similar rates of acceptable laryngeal mask airway (LMA) insertion conditions (97.3% vs 100%, respectively). However, compared to dexmedetomidine, remifentanil use was associated with a statistically significant lower movement response (27% vs 0%), a higher rate of full chin opening (73% vs 100%), and a higher rate of perfect LMA insertion conditions (56.8% vs 97.3%). This indicates that pre-administration of 2 μg·kg−1 remifentanil before induction with propofol provided better LMA insertion conditions compared to 1 μg·kg−1 dexmedetomidine.

In our study, the full chin opening rate, reported in previous studies in the propofol-dexmedetomidine group to be 95–100% [3,16,18,22], was lower (78.4%), consistent with the results of Nellore et al [17] (75%); however, the perfect or satisfactory laryngeal mask insertion condition rates were similar [3,16–18,22]. This difference may be due to evaluation differences between administrations, just as it may be related to the additional 50% N2O and 1.5–2% sevoflurane administered after induction with 90-second mask ventilation [3,22] in studies and/or the higher rate in female patients [3,16]. Stoneham et al [9] reported that intravenous lidocaine administration prior to propofol induction increased satisfactory LMA placement conditions by suppressing laryngeal reflexes and reducing the incidence of gagging, without causing a significant increase in the degree of jaw opening. Rustagi et al [16] used a similar dose and infusion protocol as in our study, and reported a higher rate of full chin opening (97.5%). However, the incidence of perfect LMA insertion conditions, which has been reported to range from 92.5% to 100% in other studies, was similar to our findings (56.7% and 62.5%, respectively). This suggests that chin opening may be a less critical determinant for LMA insertion conditions, consistent with the results of previous studies [3,18,22].

The administration of 2.0 or 2.5 mg·kg−1propofol to patients without premedication by McCollum and Dundee [36] caused 15% and 17% falls in mean systolic pressure and hypotension, respectively. Remifentanil reduces the hemodynamic response to tracheal intubation and LMA use [2,5,8,11,13,31,37]. Remifentanil is reported to be associated with significant hypokinetic cardiovascular events like higher rates of heart rate and/or arterial pressure reduction compared to other opioids [12,31,37–39]. For this reason, the bradycardia and hypotension risks increase when propofol is used with remifentanil [12]. Wilhelm et al [38] compared the effects of remifentanil (0.5 μg·kg−1·min−1 infusion 5 minutes before induction) on the induction features of propofol (2 mg·kg−1), thiopental (5 mg·kg−1), and etomidate (0.3 mg·kg−1). They reported remifentanil-propofol reduced MAP by 26%; as a result, the features related to the cardiovascular depressive effects of induction agents were clearly preserved with the remifentanil combination and the degree of depression clearly increased. The most frequent adverse effects of dexmedetomidine are hypotension and bradycardia, observed mostly in the loading period [40]. Dexmedetomidine, when administered as an IV bolus, exhibits a dose-dependent biphasic effect characterized by a transient increase in blood pressure followed by a prolonged decrease. In our study, since we administered dexmedetomidine as a 10-minute infusion, we believe that we did not observe the biphasic effect due to the loss of the hypertensive response commonly associated with rapid injection [14]. Despite dexmedetomidine causing a dose-linked fall in blood pressure with reduced plasma concentration after bolus administration, previous reports found that pretreatment with dexmedetomidine reduced the fall in blood pressure during propofol induction [15,16,19–22,33]. In our study, consistent with the results of previous studies, pretreatment with dexmedetomidine reduced the fall in blood pressure during propofol induction. When compared with baseline values, the SAP and MAP values in the dexmedetomidine group were 9% and 8% lower, respectively, after induction, while these rates were 18% and 19% in the remifentanil group. In both groups, the hemodynamic response to LMA insertion was suppressed, while the significant reductions in SAP, MAP, DAP, and HR compared to basal values continued during the study [40].

Dexmedetomidine causes an increase in bradycardia risk with increasing dose during anesthesia, with sympatholytic and preserved baroreflex effects [14,40]. Additionally, bradyarrhythmias frequently accompanying remifentanil in clinical practice were shown to be associated with temporary increase in parasympathetic tonus compared to sympathetic tonus [39]. With the myocardial depression and vasodilator effects of propofol, and the suppression of the baroreflex response, no significant increase in HR was observed, with a clear fall in arterial pressure after induction. This explains the increased bradycardia risk when dexmedetomidine or remifentanil are administered together [3,5,12,22,37,41,42]. As these negative chronotropic effects are linked to a temporary increase in parasympathetic tonus compared to sympathetic tonus, it is recommended to administer the pure anticholinergic agent of atropine with the aim of pre-emptive vagolysis before administering dexmedetomidine or remifentanil with propofol [13,22,39,42]. Additionally, in previous studies using premedication with an anticholinergic agent like glycopyrrolate or atropine before administering propofol and dexmedetomidine, the incidence of hypotension and/or bradycardia was reported to be 0–4% [13,16–18,42]. Liu et al [41] investigated the effects of different doses of dexmedetomidine (0.25, 0.5, or 1 μg·kg−1) administered 10 minutes before induction with propofol, and reported a 20% rate of bradycardia in the group receiving 1 μg·kg−1 dexmedetomidine, which they attributed to increased vagal tone. They recommended using 0.5 μg·kg−1 dexmedetomidine to reduce the risk of bradycardia. In our study, we did not administer premedication with an anticholinergic agent. In the dexmedetomidine group, bradycardia was observed in 4 patients (11.1%), while hypotension was observed in 2 patients in both groups, and 1 patient experienced both hypotension and bradycardia. Based on previous reports and our current findings, during the administration of propofol, remifentanil was associated with significant MAP depression throughout the study, whereas dexmedetomidine administration was associated with early phase (1 minute before and after LMA insertion) risks, while remifentanil has a later-phase (4 and 5 minutes after LMA insertion) HR depression risk. Therefore, in the absence of contraindications, premedication with an anticholinergic agent or opting for a lower dose of dexmedetomidine or remifentanil before induction with propofol may be more appropriate to ensure more stable hemodynamics by reducing the risk of bradycardia and/or hypotension [41].

Remifentanil has shorter apnea duration compared to other opioids due to its ultra-short effect duration [2,42]. Dexmedetomidine causes dose-dependent sedative and hypnotic effects mimicking natural sleep without causing clinically significant respiratory depression by preventing norepinephrine (NE) release through presynaptic activation of the alpha-2 adrenoreceptor on locus ceruleus [15,33]. In our study, we found the apnea duration was significant shorter in the dexmedetomidine group compared to the remifentanil group (282 seconds vs 358 seconds, respectively) [3,16,18,22]. This may be mostly related to the apnea duration in the dexmedetomidine group being linked to the depressant effect of propofol, equivalent to the strengthening of the depressant effects of opioids on respiration by propofol. Additionally, the apnea duration in the dexmedetomidine group was consistent with previous studies. In the study by Üzümcügil et al [3], despite using a lower dose of propofol for induction (1.5 μg·kg−1), the apnea duration was similar to that in our study. This may be related to the higher proportion of female patients in the study by Üzümcügil et al [3] and the administration of 50% N2O and 1.5% sevoflurane with 90 seconds of mask ventilation after induction.

In our study, the duration to eyelash reflex loss was shorter with remifentanil administration (26.1 seconds) compared to dexmedetomidine administration (31.6 seconds). In a study evaluating the effects of remifentanil or fentanyl on the induction features of propofol, thiopental, or etomidate, Wilhelm et al [38] reported the duration to eyelash reflex loss was significantly shorter with remifentanil administration in the induction process compared to fentanyl administration, and concluded that remifentanil improved the induction duration and induction quality. The much shorter time to loss of eyelash reflex in the remifentanil group compared to the study by Wilhelm et al [38] (50.2 seconds) may be related to the higher dose of propofol used for induction, the addition of 0.03 mg·kg−1 midazolam before induction, and the use of a high-dose bolus instead of infusion for remifentanil. Although we cannot clearly assess it due to the lack of a control group in our study, when the duration for control groups in previous reports is evaluated, the time to loss of eyelash reflex was lower in both groups; however, the administration of remifentanil improved induction duration and quality more than with dexmedetomidine administration [35,43]. Previous studies reported the mean LMA insertion duration was 6–38 seconds [24,27]. This inconsistency in time may be associated with patient age, experience of the inserter, LMA type, insertion technique, time calculation method, and agents used for induction not being in the same group. Compatible with previous report results, with the improvement in LMA insertion conditions, we found the LMA insertion duration was significantly shorter with remifentanil administration (mean 13.7 seconds) compared to dexmedetomidine (mean 16 seconds) administration [2,27].

Although doses higher than 1 μg·kg−1 of remifentanil were reported to be associated with clinically significant muscle rigidity with rapid administration as a bolus, consistent with the results of previous studies with similar drug combinations and dosages, no patient had symptoms of rigidity linked to opioids [2,5,12,31]. We believe that our pretreatment with benzodiazepines and slow administration of remifentanil over 60 second with 30 seconds of hypnotic agent administration prevented opioid-derived rigidity [5].

Insertion of the laryngeal mask airway (LMA) requires sufficient mouth opening and sufficient depth of anesthesia to suppress airway reflexes like coughing, retching, and laryngeal spasm [32]. Additionally, the propofol, dexmedetomidine, and remifentanil doses required to obtain sufficient anesthesia depth display individual differences. As a result, administration of a fixed dose may cause airway complications and cardiorespiratory depression linked to surficial or deep anesthesia [15,32,33]. During dexmedetomidine infusion, it is difficult to predict anesthesia depth and requirements with changes mediated by the autonomic nervous system [44]. The bispectral index is used to measure anesthesia depth by processing electroencephalography. It ensures titration of the anesthetic agents according to anesthesia depth [45]. In our study, LMA insertion was performed 90 seconds after induction by monitoring anesthesia depth using the BIS, with additional doses administered as needed when the BIS value was below 40. We believe this approach allowed us to mitigate the variability in LMA insertion timing associated with operator assessment, as well as differences in anesthesia depth resulting from patient-specific dose requirements. By standardizing dose administration, we were able to minimize variations in LMA insertion conditions linked to changes in anesthesia depth.

Airway injuries are well-known complications of general anesthesia (GA). Among cases related to airway injuries, nearly 33% involve airway trauma causing long-term pain or voice problems, linked mostly to nerve apraxia and cartilage trauma [46]. One of the advantages of supraglottic airway devices is their much lower incidence of pharyngolaryngeal morbidity compared to endotracheal intubation [47]. Throat pain is rated as the eighth most common adverse effect in the postoperative period after GA, contributing to postoperative morbidity and patient dissatisfaction [47]. After LMA insertion, the general incidence of postoperative throat pain varies over a large range of 0–43% and can cause patient dissatisfaction with anesthesia [24]. Several variables affect the pharyngeal morbidity incidence due to LMA. The most common cause of airway morbidity with LMA is trauma during insertion [24]. There may be many factors affecting throat pain linked to LMA, and the incidence can be affected by anesthesia depth during insertion, use of neuromuscular blocker drugs, insertion method, experience of the inserter, number of attempts, large-size LMA, high cuff volume or cuff pressure, anesthesia duration, type of postoperative analgesia, increased cuff pressure linked to N2O diffusion from the cuff wall, and presence of a heated moisture exchanger in the circuit [24,47]. In a study evaluating the effect of low-dose mivacurium administration on LMA insertion conditions, Chui et al [30] reported that throat pain incidence fell from 53% to 24% along with a reduction in the incidence of adverse reactions and increase in LMA ease of insertion. Venugopalve et al [47] reported 33% dysphagia, 38.2% presence of blood, and 35% throat pain (with 5% severe), when using LMA in studies comparing the whole pharyngolaryngeal morbidity (PLM) spectrum for LMA and ETT. In both Group R and Group D in our study, we believe the lower general averages for dysphagia (5.4%, 13.9%), presence of blood (5.4%, 16.7%), and throat pain (13.5%, 22.2%) are due to LMA insertion with sufficient anesthesia depth, cuff pressure being stabilized to 60 mmHg, and the experience of the inserters. The lack of significant differences between the groups may be related to the reduction in the number of attempts along with the improvement in LMA insertion conditions, reducing pharyngeal morbidity incidence with remifentanil administration.

One of the limitations of our study is that our results are only valid for patients aged 18–65 years in ASA classes I and II. Patients in ASA classes III or IV may have different hemodynamic tolerance to administration of high doses like 2 μg·kg−1 of remifentanil or 1 μg·kg−1 dexmedetomidine, especially in those with serious heart disease or in unpremedicated or anxious patients such as those undergoing emergency surgeries. However, since the pharmacokinetics and pharmacodynamics of dexmedetomidine, propofol, and remifentanil change with age, the doses we used are not applicable to older adult [15,19,32]. The absence of a control group in our study may be considered a limitation. However, the risk of airway trauma and inadequate ventilation can increase if pharyngolaryngeal reflexes are not sufficiently suppressed by the administration of propofol alone. We did not establish a control group, as we considered this to be unethical.

Conclusions

In conclusion, this study demonstrated that in healthy, premedicated patients with appropriate airway anatomy, the administration of 2 μg·kg−1 remifentanil before induction with 2.5 mg·kg−1 propofol, compared to 1 μg·kg−1 dexmedetomidine, resulted in significantly greater suppression of MAP without increasing the risk of bradycardia or hypotension. It also provided longer apnea duration, shorter LMA placement time, shorter eyelash reflex loss duration, and a similar rate of acceptable LMA placement conditions (100% vs 97.3%, respectively), along with a higher rate of perfect LMA placement conditions (97.3% vs 56.8%, respectively). Although remifentanil caused significantly more hemodynamic depression than dexmedetomidine, the incidence of bradycardia and hypotension was higher with dexmedetomidine (19.4% vs 8.1%, respectively), although this difference was not statistically significant. Based on these findings, we believe that during dexmedetomidine administration, slow infusion combined with premedication using an anticholinergic agent, in the absence of contraindications, or opting for a lower dose, would be more suitable for ensuring more stable hemodynamics by reducing the risk of bradycardia and/or hypotension.