Comparison of Remimazolam and Dexmedetomidine for Sedation in Awake Endotracheal Intubation in Scoliosis Surgery: A Retrospective Analysis

Introduction

Scoliosis is described as aberrant curvature and rotation of the spine. Scoliosis can be idiopathic or caused by other diseases and is usually diagnosed when patients are at a young age [1]. Patients with scoliosis often have varying degrees of cardiopulmonary dysfunction, pain, and low quality of life. Surgical correction is an effective way to improve a patient’s condition. In particular, patients with a large Cobb angle (≥50°) and rapid progress (≥10° per year) should consider surgery [2]. Awake endotracheal intubation (AEI), also known as awake tracheal intubation [3], is often required during surgical anesthesia in patients with scoliosis, due to abnormal head and neck motion or postoperative placement of external stents that restrict head and neck motion [4].

AEI is still the most widely accepted strategy for an expected difficult airway, owing to the high security and success rate [5]. Although AEI can be conducted with only local anesthesia, sedation is commonly applied during the procedure to alleviate stress and improve patients’ cooperation. Remifentanil and dexmedetomidine are highly recommended sedatives [5,6]. However, there are some concerns about the 2 drugs. Remifentanil, one kind of opioid, significantly depresses the respiratory system [7,8], which is extremely risky for patients with scoliosis. Dexmedetomidine invariably leads to bradycardia by inhibiting norepinephrine release and sympathetic nervous system activity [9,10]. Moreover, dexmedetomidine-induced bradycardia can even cause cardiac arrest in high-risk patients [11]. Thus, a novel strategy for AEI is needed.

Remimazolam, a benzodiazepine, has been widely recognized by anesthesiologists for its effectiveness and safety [12,13]. More importantly, it has little effect on the cardiovascular system and spontaneous respiration [14,15]. In addition, Murata et al reported a case in which the patient completed awake craniotomy and showed good tolerance after discontinuation of remimazolam [16]. Therefore, remimazolam is an ideal candidate for AEI sedation. However, studies on AEI sedation with remimazolam for scoliosis surgery are still lacking. Therefore, this retrospective study aimed to compare sedation with remimazolam during AEI with dexmedetomidine in 98 patients undergoing surgery for scoliosis between January and December 2023.

Material and Methods

ETHICS STATEMENT:

This study was designed as a retrospective study, since rectifying surgery for scoliosis has been suspended in our institution for various reasons. Ethics issue for this was approved by the Ethics Committee of the Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital). The approval number is YJ-2024-020. Written informed consent was not required.

RETROSPECTIVE DATA SOURCE:

Adult patients who underwent scheduled correction surgery for scoliosis with AEI were considered eligible. Medical records for these patients from January 1, 2023, to December 31, 2023, at our hospital were extracted to establish the database. The reason for the timespan is that remimazolam was first used in AEI after January 1, 2023, and the surgery was suspended on January 1, 2024. According to the records and our habit of AEI sedation, 2 groups were established: remimazolam group (AEI with remimazolam) and dexmedetomidine group (AEI with dexmedetomidine). Cases of patients with incomplete data reports or pre-administration of other sedatives and those with preoperative hypoxia or hypertension were excluded.

DESCRIPTION OF AEI:

After entering the operation room, patients were routinely monitored with electrocardiograph, SpO₂, invasive blood pressure (IBP), and bispectral index (BIS). Dexmedetomidine or remimazolam was the sedative for patients. Accordingly, patients were divided into the dexmedetomidine group and remimazolam group when we retrospectively screened the medical records. Ten minutes before intubation, dexmedetomidine (Yangtze River Pharmaceutical Group, Jiangsu, China) was continuously pumped with a dosage of 1 ug/kg (ie, the rate for a patient of 50 kg is 300 ug/h), and methylprednisolone (Pfizer Manufacturing Belgium NV, Belgium) 40 mg, penehyclidine (Nhwa Pharmaceutical Cooperation, Jiangsu, China) 0.01 mg/kg, and ramosetron (Lummy Pharmaceutical Cooperation, Chongqing, China) 0.3 mg were injected via peripheral venous administration. Tetracaine mucilage (Lijun Pharmaceutical Cooperation, Xi’an, China) 5 mL was then applied to perform the surface anesthesia of the mouth and throat. Five minutes before intubation, sufentanil (Humanwell Healthcare, Yichang, China) 0.01 ug/kg was administered intravenously. One minute after performing cricothyroid membrane puncture and rapid endotracheal injection of 1% lidocaine (Harvest Pharmaceutical Cooperation, Shanghai, China) 2 mL, endotracheal intubation was conducted with the guidance of a fiber bronchoscope. Remimazolam (Hengrui Medicine, Jiangsu, China) 0.05 mg/kg was injected when performing cricothyroid membrane puncture and injection of lidocaine 1 min before intubation. For unsuccessfully intubated cases, intubation was performed again upon SpO₂ rising to baseline. The patients were sent back to the ward after 3 failed attempts, and the surgery was delayed.

OUTCOMES:

The primary outcome was successful AEI rate of the first attempt. The secondary outcomes were as follows: (1) time to successful AEI (from AEI procedure initiation to successful intubation), (2) number of attempts to AEI, (3) mean arterial pressure (MAP) change (from sedative administration to intubation, and before and after intubation), (4) heart rate (HR) change (from sedative to the moment before intubation, and from the moment before intubation to intubation procedure), (5) BIS value before and during intubation, (6) successful rate of AEI, (7) incidence of hypoxia before intubation initiation, and (8) the first value of end-tidal CO₂ (EtCO₂) after intubation. These data were collected from electronic records of the Anesthesia Information Management System.

DATA EXTRACTION:

Two investigators blinded to the group assignments screened each case separately to determine the eligibility of the records, and subsequently, extracted the related data. Disagreements between the investigators were settled by discussion or by consulting an attending expert. All investigators were well trained. A senior investigator did a spot check to verify the reliability of the data.

STATISTICAL ANALYSIS:

EpiData 3.1 was used to input the extracted data, and the data were imported into SPSS 26.0 for storage and analysis. Categorical variables, such as successful rate of AEI and incidence of hypoxia before intubation initiation, were expressed as the number of cases (percentage) and analyzed by the chi-square test. The measurement data were first tested for normality (Kolmogorov-Smirnov test). The variables with a normal distribution, such as MAP, HR, BIS, and EtCO₂, were expressed as mean ± standard deviation (SD) and analyzed by independent-sample t tests. Variables that did not follow normal distribution, such as time to successful AEI, were expressed as median (interquartile range) and analyzed the non-parametric Mann-Whitney U test. The significance level was set at P<0.05.

Results

COMPARISON OF BASELINE:

The demographic data were comparable between the remimazolam group and dexmedetomidine group, including sex, age, height, body mass index (BMI), and Mallampati classification, although the weight of the remimazolam group was higher than that of the dexmedetomidine group (44.22±5.42 vs 42.05±4.04 kg, P=0.031) (Table 1).

COMPARISON OF AEI-RELATED INDICATORS:

The successful AEI rate of the first attempt was 70.91% (39/55) in the remimazolam group and 65.12% (28/43) in the dexmedetomidine group, with no significant difference between the 2 groups (P=0.541, Figure 3A). There were 3 cases of failure to conduct AEI, with 1 in the remimazolam group and 2 in the dexmedetomidine group (Figure 3B). The reason in the medical records was described as difficult glottis exposure. The overall success rate of AEI had no significant difference between the groups (98.18% vs 95.35%, P=0.580, Figure 3B). According to the practice guideline in our department, endotracheal intubation should not be conducted more than 3 times; therefore, the 3 patients had failed attempts in AEI. They were sent back to the ward, as the medical records documented, and their surgeries were delayed. The attempt times to successful AEI were similar in both groups (1(1,2) vs 1(1,2), P=0.487). Figure 3C shows the cases of different attempts. Also, there was no significant difference in the total time taken by anesthesiologists to conduct AEI between the groups (11(11,14) vs 11(11,15) min, P=0.535, Figure 3D).

COMPARISON OF HEMODYNAMICS:

After administration of remimazolam or dexmedetomidine, the blood pressure (BP) of the patients was significantly decreased. In comparison with that in the dexmedetomidine group, the decrease of MAP in the remimazolam group was significantly less during sedation and the moment before intubation (8.33±2.28 vs 11.30±1.86 mmHg, P<0.001, Figure 4A). Moreover, when conducting intubation, the increase of MAP in the remimazolam group was lower than that of the dexmedetomidine group (7.40±2.81 vs 9.26±5.08 mmHg, P=0.024, Figure 4B). In comparison with that of dexmedetomidine, the decrease of HR caused by remimazolam was significantly lower before intubation (2.85±1.82 vs 12.28±2.50 beats/min, P<0.001, Figure 4C). However, the increase of HR induced by remimazolam was similar to that of dexmedetomidine (7.53±5.41 vs 8.37±5.31 beats/min, P=0.441, Figure 4D).

COMPARISON OF DEGREE OF SEDATION AND RESPIRATORY EVENTS:

The BIS value was equivalent between the remimazolam and dexmedetomidine groups, whether before intubation or during intubation (82.65±1.89 vs 82.33±1.82, P=0.387; 90.75±3.03 vs 91.05±3.17, P=0.634, respectively, Figure 5). Although some patients had hypoxia after the sedative, the difference was not significant (9.09% vs 18.60%, P=0.168, Figure 6A). In addition, there was no significant difference in the first EtCO2 after successful intubation (41.78±2.89 vs 41.49±3.40 mmHg, P=0.654, Figure 6B).

Discussion

We conducted a retrospective study on the comparison of remimazolam and dexmedetomidine in AEI. The results indicated that AEI could be successfully performed under remimazolam or dexmedetomidine sedation, but remimazolam was associated with more stable hemodynamics.

AEI is still regarded as the foremost choice for a difficult airway [17]. Successful AEI is determined by the airway anatomy of patients, dexterity of operators, operating apparatus, and well-controlled stimulation. It has been reported that over 90% of patients with an anticipated difficult airway can undergo successful AEI with proper methods [18,19]. The result of this study is consistent with these reports. Under the procedure of our institution, overall success rate of the first attempt was comparable in the remimazolam group and the dexmedetomidine group. We gave up trying a fourth time, as repeated intubation increases the likelihood of injury, bleeding, and edema [20,21].

Nevertheless, patients are commonly distressed due to the intensive stimulation induced by AEI. In spite of propofol and local anesthesia, patients can still experience nausea or bucking [22]. Sedation can make it a more tolerable and comfortable process for the patients, especially for those who are particularly anxious or sensitive. Moreover, the stimulation can lead to huge hemodynamic fluctuation, such as a sudden increase of BP and tachycardia. It is reported that AEI under local anesthesia and sedation with midazolam and fentanyl can lead to significant hemodynamic changes (HR increase >20 beats/min, systolic BP increase >20 mmHg), and the changes last for more than 5 min [23]. In our study, sedation under either remimazolam or dexmedetomidine combined with local anesthesia effectively suppressed intubation-induced stress, as the increase of HR and MAP was less than 10 beats/min and 10 mmHg, respectively. However, the dexmedetomidine-induced decrease of MAP after sedation and intubation-induced increase of MAP were significantly larger than that of remimazolam, which means remimazolam performed better in minimizing BP fluctuation. Also, remimazolam had little effect on HR, while dexmedetomidine caused significant decreases in HR. Recently, the continuous administration of remimazolam for AEI was successfully performed in maxillofacial surgery; however, the results indicated no significant differences in hemodynamic parameters between dexmedetomidine and remimazolam [24]. The different effects may be attributed to the cardiopulmonary dysfunction of patients with scoliosis [25].

Sedatives can result in hypoventilation, and some vulnerable patient’s conditions even deteriorate into resultant hypoxia and hypercarbia [26,27]. According to the records, 5 patients in the remimazolam group and 8 in the dexmedetomidine group had hypoxia that could be rectified by reminding the patients to breathe deeply. The first value of EtCO2 after intubation was far lower than the upper limit of the normal range, which further proves the steerable and safe sedation induced by remimazolam or dexmedetomidine.

The primary limitation of this study is the study design. The optimal design to compare remimazolam with dexmedetomidine in AEI is a prospective randomized trial. In this way, the tolerance degree can be directly reflected by evaluating patient responses, such as patient discomfort scores and post-intubation scores [28,29]. The present study was designed as a retrospective study because scoliosis correction was suspended this year in our hospital. Another limitation is that the relatively low prevalence of scoliosis and limited timespan lead to the small sample size. Even so, the present study can provide preliminary results, and further studies should be conducted.

Conclusions

This retrospective study indicates that both remimazolam and dexmedetomidine sedation combined with local anesthesia can facilitate AEI for patients with scoliosis. However, remimazolam is associated with more stable hemodynamics. Prospective randomized trials are needed to verify our findings.