Abstract
Objective
To compare the effects of two different administration methods of dexmedetomidine (DEX) used as an adjuvant to ropivacaine in ultrasound-guided bilateral intermediate cervical plexus block (CPB) in terms of efficacy and the duration of postoperative analgesia in patients undergoing ambulatory thyroidectomy.
Methods
This double-blind, randomized study enrolled patients who underwent thyroidectomy with ultrasound-guided bilateral intermediate CPB. Patients were randomized to receive either perineural administration of dexmedetomidine (group DP) or intravenous pumping of dexmedetomidine (group DI). The 40-item Quality of Recovery (QoR-40) questionnaire was used to assess the primary endpoint, which was the global QoR-40 score 24 h after the operation.
Results
Sixty patients were randomized equally into the two groups. The total QoR-40 score 24 h postoperatively was significantly higher in group DP than group DI (160.6 ± 9.1 versus 152.8 ± 7.9, respectively). Dimensions of physical comfort and pain scores were significantly higher in group DP than group DI. The visual analogue scale pain score scores were significantly lower in group DP than group DI at 12 and 24 h postoperatively.
Conclusions
DEX as an adjuvant to ropivacaine in ultrasound-guided intermediate CPB can improve the QoR-40 score and prolong postoperative analgesia.
Trial registration number: ChiCTR2000031264 at www.chictr.org.cn on 26 March 2020.
Introduction
Surgery is the most effective treatment for thyroid tumours, but pain and postoperative nausea and vomiting are considered two of the most feared complications for patients undergoing thyroid surgery, which decreases the quality of their postoperative recovery. Day surgery, same-day discharge and rapid postoperative recovery pose new challenges to anaesthesiologists. 1 Postoperative pain is a key component of recovery following surgery. Currently, general anaesthesia combined with regional nerve block technology is widely used in clinical practice. Ultrasound-guided intermediate cervical plexus block (CPB) is a simple and easy technique, and some studies have confirmed its effectiveness.2,3
Various adjuvants that prolong the duration of peripheral nerve blocks are used in clinical practice. Dexmedetomidine (DEX) is an adrenoreceptor agonist that selectively acts on the adrenoreceptor alpha-2 receptor and is used as an analgesic, sedative and antianxiety agent, with minimal risk for respiratory depression,4,5 DEX is available in a variety of modes of administration, including intranasal, intravenous and perineural injections. 6 The intravenous infusion of DEX decreases postoperative narcotic administration and prolongs analgesia; 7 and it reduces the incidence of postoperative delirium and cognitive dysfunction. 8 In addition, studies have shown that local application of DEX, as a nerve blocking anaesthetic, can prolong nerve block duration, improve the postoperative analgesic effect and stabilize the haemodynamics.9,10 Local application can also significantly reduce the related complications caused by intravenous application, such as sinus bradycardia and hypertension, 11 with higher safety. However, studies on the analgesic effects of the intravenous and perineural administration of DEX have been inconsistent. In a study, when DEX was used as a local anaesthetic ropivacaine adjuvant for supraclavicular brachial plexus block, there was no difference in the duration of block analgesia between systemic and perineural administration. 12 More recent evidence indicates that perineural DEX improves brachial plexus block onset, quality and analgesia. 13 Moreover, there is also no clear information on the mode of administration of DEX, which is better in ultrasound-guided intermediate CPB. This current study compared the effects of different administration methods of DEX on the efficacy of ultrasound-guided intermediate CPB and the duration of postoperative analgesia to improve the quality of postoperative recovery in patients undergoing ambulatory thyroidectomy.
Patients and methods
Study design
This double-blind, randomized clinical trial recruited patients who underwent elective total thyroidectomy at the Department of Anaesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China between August 2020 and April 2021. The inclusion criteria were as follows: (i) aged 18–60 years; (ii) American Society of Anesthesiologists physical conditions of I–II; (iii) body mass index between 18–30 kg/m2; (iv) underwent elective total thyroidectomy (with normal thyroid function tests). The exclusion criteria were as follows: (i) patients with known coagulation dysfunction; (ii) a history of local anaesthetic allergy; (iii) a history of infection at the puncture site; (iv) a history of abuse of pain medications; (v) sinus bradycardia; (vi) atrioventricular block. The reporting of this study conforms to the CONSORT guidelines. 14
Ethical approval for this study (no. PJ2020-07-08) was provided by the Institutional Ethics Committee of The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China, in June 2020. The study was registered with the Chinese Clinical Trial Registry (ChiCTR2000031264). All study participants provided written informed consent.
Randomization and masking
All patients were randomly divided into two groups in a 1:1 ratio using computer-generated random numbers. The results of the randomized group allocations were enclosed in a sealed opaque envelope that could only be opened only by an anaesthesiologist who was not involved in the study. The observer who collected the perioperative data and the patient were unaware of the anaesthesia technique being performed. The anaesthetic nurse prepared all of the study solutions using an aseptic technique. According to their randomized group allocation, patients received either perineural or intravenous DEX. The two groups received the following: (i) patients that received perineural administration of DEX (group DP) were administered 0.5 μg/kg DEX combined with 0.33% ropivacaine to 20 ml for ultrasound-guided intermediate CPB and intravenous pumping of normal saline 20 ml at the beginning of the block; and (ii) patients that received intravenous pumping of DEX (group DI) were administered 0.33% ropivacaine 20 ml for ultrasound-guided intermediate CPB and 20 ml of 0.5 μg/kg DEX that was injected intravenously at the beginning of the block. DEX hydrochloride (0.1 mg/ml) was obtained from Yangtze River Pharmaceutical Group, Taizhou, Jiangsu Province, China.
Study treatments
During the preoperative evaluation conducted 1 day before the operation, all participants were informed about the procedure, benefits and study-related risks of the operation, and then written informed consent was obtained from all participants.
All patients fasted before the surgery. After arrival to the operating room and ensuring peripheral venous access, routine monitoring was performed, including noninvasive blood pressure and five-lead electrocardiography with peripheral capillary oxygen saturation attached. An ultrasound-guided (linear high-frequency probe, 3–13 MHz; SonoSite M-Turbo®, FUJIFILM Sonosite, Bothell, WA, USA) bilateral intermediate CPB was performed by two anaesthesiologists (J.R. and C.C.) experienced in the technique before general anaesthesia. The patients in both groups were placed in the supine position with their heads turned to the opposite side and received standard skin disinfection. The transducer probe was placed transversely over the midpoint of the sternocleidomastoid muscle such that the tapering posterior edge was positioned in the middle of the screen (at the level of the cricoid cartilage, where the external jugular vein crosses the sternocleidomastoid). With the in-plane technique, the block needle was advanced adjacent to the superficial cervical plexus in the plane deep to the sternocleidomastoid, underneath the investing fascia (sternocleidomastoid‑trapezius fascia) and immediately above the interscalene groove. After negative aspiration, in group DP, half of the mixture of 0.5 μg/kg DEX combined with 0.33% ropivacaine to 20 ml was injected under the fascia (Figure 1) and the block was repeated on the other side. Normal saline (20 ml) was intravenously pumped at the beginning of the block within 10 min. In group DI, the patients received the same and were injected with a total of 20 ml of 0.33% ropivacaine for ultrasound-guided intermediate CPB. Simultaneously, 20 ml of 0.5 μg/kg DEX was injected intravenously at the beginning of the block within 10 min. At 20 min after block implementation, the sensory block at the surgical incision site was tested by the pinprick method using a 25G hollow needle. Block success was defined as blunted or loss of sensation compared with the unblocked anatomic area.

An ultrasound image of the ultrasound-guided intermediate cervical plexus block showing the spread of the injectate below the investing fascia. SCMM, sternocleidomastoid muscle; PF, prevertebral fascia; ICA, internal carotid artery; ECA, external carotid artery; C4-TP, transverse process of the fourth cervical vertebra. The arrow points to the spread of the injectate.
After preoxygenation for 3 min, general anaesthesia was induced with a close-fitting mask for oxygen delivery at a rate of 6 l/min. Subsequently, intravenous injections of 0.1 mg/kg dezocine, 2–3 mg/kg etomidate, 0.3–0.4 µg/kg sufentanil and 0.2–0.3 mg/kg cisatracurium were administered to ensure smooth endotracheal intubation. Anaesthesia was maintained using 4–6 mg/kg/h of propofol and 0.1–0.2 µg/kg/min remifentanil, with intermittent injections of 0.1–0.2 mg/kg cisatracurium intraoperatively when needed. The concentrations of plasma propofol and remifentanil were adjusted to maintain the depths of anaesthesia to keep the bispectral index system value between 40 and 60. At the end of surgery, every patient in each group was intravenously injected with 10 mg azasetron and 50 mg flurbiprofen axetil. The monitoring of vital signs was continued for patients with a heart rate of <50 beats per minute and 0.5 mg atropine was administered. A total of 3–6 mg ephedrine was given intravenously to treat hypotension for a mean arterial pressure of <60 mmHg or <30% of the baseline. Patients were admitted to the postanaesthesia care unit (PACU) after surgery. Patients were extubated in the PACU according to the standard extubation protocol and when the Steward recovery score exceeded 4 points, patients were transferred to the postoperative ward. An antiemetic (10 mg azasetron) and a painkiller (50 mg flurbiprofen axetil) were given 12 h after surgery on the postoperative ward. For patients with a visual analogue scale (VAS) pain score ≥ 4, 50 mg flurbiprofen was administered intravenously as a rescue analgesic.
Study outcomes
The 40-item Quality of Recovery (QoR-40) questionnaire was used to assess the primary endpoint, which was the global QoR-40 score 24 h after the operation. 15 The dimensions of the QoR-40 represent good quality recovery after anaesthesia and surgery; and they include the patient’s emotional state (nine items), physical comfort (12 items), physical independence (five items), psychological support (seven items) and pain (seven items), comprising a total of 40 items. 15 Positive items are scored from 1 (worst) to 5 (best), scores are reversed for negative items, and scores range from 40 (extremely poor QoR) to 200 (superb QoR). 15 The higher the score is, the better the QoR. All patients completed the questionnaire at two time points: 24 h preoperatively and 24 h postoperatively.
Secondary endpoints were the VAS scores at 0 (immediately after extubation) and 4, 8, 12 and 24 h after surgery; and the number of patients requiring rescue analgesia. Furthermore, intraoperative haemodynamic parameters, including the mean arterial pressure (MAP) and heart rate (HR), were recorded at five time points: T0, baseline level when entering the operating room; T1, immediately after incision; T2, when the upper pole of the thyroid was separated; T3, end of the surgery; T4, extubation. The incidence of postoperative nausea and vomiting were also recorded and properly managed. Other complications related to the operation, such as somnolence, hypotension, bradycardia and Horner’s syndrome were also documented and managed.
Statistical analyses
The sample size estimation was based on global QoR-40 scores. As reported, the minimal clinically important difference is 6.3 points for the QoR-40, which signifies a clinically important difference. 16 According to our unpublished pilot study, the mean ± SD QoR-40 score at 24 h after surgery was equivalent to 152.0 ± 7.2. The sample size calculation revealed that 28 patients per group were required to achieve a 90% power and a 5% significance level. Ultimately, to allow for a 10% dropout rate, 62 patients were enrolled.
All statistical analyses were performed using IBM SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY, USA). GraphPad Prism 8 (Graphpad Software Inc., San Diego, CA, USA) was used for figure rendering. Continuous variables are reported as the mean ± SD or median (interquartile range). Independent t-test was applied to analyse continuous variables of normally distributed data between the two groups. Mann–Whitney U-test was used for data with skewed distributions. Categorical variables are presented as n (%) and were analysed using χ2-test or Fisher’s exact test. A P-value <0.05 was considered statistically significant.
Results
A total of 62 patients were enrolled in this study, of whom one was excluded in each group due to refusal to participate. The remaining 60 patients were randomly divided into the two groups (Figure 2). The baseline clinical characteristics of all patients and the preoperative global QoR-40 score are summarized in Table 1. There were no significant differences between groups DP and DI in terms of the preoperative data.

Flow diagram showing patient numbers at various stages in a single-centre, double-blind, randomized trial that was conducted on adult patients undergoing ambulatory thyroidectomy to compare the effects of two different administration methods of dexmedetomidine (DEX) on the efficacy of ultrasound-guided intermediate cervical plexus block and the duration of postoperative analgesia. DP, perineural administration of DEX; DI, intravenous pumping of DEX.
Baseline clinical and demographic characteristics and preoperative global 40-item Quality of Recovery (QoR-40) questionnaire scores in the two study groups investigated in a single-centre, double-blind, randomized trial that was conducted on adult patients (n = 60) undergoing ambulatory thyroidectomy to compare the effects of two different administration methods of dexmedetomidine on the efficacy of ultrasound-guided intermediate cervical plexus block and the duration of postoperative analgesia.
Data presented as mean ± SD or n of patients.
No significant between-group differences (P ≥ 0.05); continuous data were compared using independent t-test; categorical data were compared using χ2-test.
DP, perineural administration of dexmedetomidine; DI, intravenous pumping of dexmedetomidine; BMI, body mass index; ASA, American Society of Anesthesiologists; NYHA, New York Heart Association.
There were no significant differences between groups DP and DI in terms of the intraoperative variables, such as consumption of intraoperative medication, duration of anaesthesia, duration of surgery and extubation time (Table 2). In particular, seven patients in group DI developed postoperative nausea and five of them experienced vomiting. In group DP, five patients had nausea and four of them had vomiting. However, these differences in nausea and vomiting were not significant between the two groups.
Comparison of the intraoperative variables and postoperative nausea and vomiting between the two study groups investigated in a single-centre, double-blind, randomized trial that was conducted on adult patients (n = 60) undergoing ambulatory thyroidectomy to compare the effects of two different administration methods of dexmedetomidine on the efficacy of ultrasound-guided intermediate cervical plexus block and the duration of postoperative analgesia.
Data presented as mean ± SD or n of patients (%).
No significant between-group differences (P ≥ 0.05); continuous data were compared using independent t-test; categorical data were compared using χ2-test.
DP, perineural administration of dexmedetomidine; DI, intravenous pumping of dexmedetomidine.
Haemodynamic parameters, including MAP and HR, were recorded at five time points (T0, baseline level when entering the operating room; T1, immediately after incision; T2, when the upper pole of the thyroid was separated; T3, end of the surgery; T4, extubation). HR decreased from T1 to T4 in both groups, with the decrease in group DI being more obvious than that in group DP, but these differences were not significant between the two groups (Figure 3). No significant difference was observed between the groups in terms of the MAP.

Changes in haemodynamic parameters in the two study groups investigated in a single-centre, double-blind, randomized trial that was conducted on adult patients (n = 60) undergoing ambulatory thyroidectomy to compare the effects of two different administration methods of dexmedetomidine on the efficacy of ultrasound-guided intermediate cervical plexus block and the duration of postoperative analgesia: (a) mean arterial pressure (MAP) and (b) heart rate (HR). Data presented as mean ± SD. DP, perineural administration of dexmedetomidine; DI, intravenous pumping of dexmedetomidine; T0, baseline level when entering the operating room; T1, immediately after incision; T2, when the upper pole of the thyroid was separated; T3, end of the surgery; T4, extubation.
The global scores of the QoR-40 at 24 h after the operation were significantly higher in group DP than in group DI (160.6 ± 9.1 versus 152.8 ± 7.9, respectively; P = 0.001) (Table 3). Among the five dimensions, the scores in the dimensions of physical comfort and pain were significantly higher in group DP than in group DI (P < 0.001 for both comparisons). The postoperative VAS pain scores were significantly lower in group DP than in group DI at 12 h and 24 h after surgery (P < 0.05) (Table 4). No rescue analgesia was required in either group. There were no intermediate CPB-related adverse reactions, such as hypotension, bradycardia and Horner’s syndrome, observed in the study.
Comparison of the 40-item Quality of Recovery (QoR-40) questionnaire scores at 24 h after surgery between the two study groups investigated in a single-centre, double-blind, randomized trial that was conducted on adult patients (n = 60) undergoing ambulatory thyroidectomy to compare the effects of two different administration methods of dexmedetomidine on the efficacy of ultrasound-guided intermediate cervical plexus block and the duration of postoperative analgesia.
Data presented as mean ± SD.
Continuous data were compared using independent t-test; NS, no significant between-group difference (P ≥ 0.05).
DP, perineural administration of dexmedetomidine; DI, intravenous pumping of dexmedetomidine.
Comparison of the postoperative visual analogue scale pain scores between the two study groups investigated in a single-centre, double-blind, randomized trial that was conducted on adult patients (n = 60) undergoing ambulatory thyroidectomy to compare the effects of two different administration methods of dexmedetomidine on the efficacy of ultrasound-guided intermediate cervical plexus block and the duration of postoperative analgesia.
Data presented as median (interquartile range).
Continuous data were compared using Mann–Whitney U-test; NS, no significant between-group difference (P ≥ 0.05).
DP, perineural administration of dexmedetomidine; DI, intravenous pumping of dexmedetomidine.
Discussion
This current double-blind, randomized clinical trial demonstrated that perineural DEX (0.5 μg/kg) improved the global QoR-40 at 24 h after the operation, especially in the dimensions of physical comfort and pain. During thyroid surgery, the abundant and complicated network of blood vessels and nerves around the thyroid glands, and the use of anaesthetics and analgesics, make it necessary for surgeons to focus on the effects of these factors on the circulatory system and postoperative recovery. Simultaneously, there may be serious adverse reactions, such as delayed recovery after surgery, restlessness, and nausea and vomiting; and patients often suffer from moderate-to-severe incisional pain and especially cough and odynophagia, causing discomfort. 17 Several techniques are used to reduce postoperative pain after thyroid surgery, including systemic opioids, nonsteroidal anti-inflammatory drugs, superficial CPB and deep CPB; and these techniques have been performed in almost all studies using anatomical landmarks.18,19 The intermediate CPB is believed to provide more profound analgesia, especially for deep structures that may have an autonomic sympathetic or ‘visceral’ pain distribution. Moreover, compared with deep blocks, the risk of developing complications such as phrenic nerve palsy, Horner’s syndrome and subarachnoid or epidural injection is very low with intermediate blocks. 20
Dexmedetomidine can be administered through a variety of routes. 21 During intravenous administration, DEX should be pumped slowly and at regular intervals. Large-dose and rapid intravenous injections of the drug will induce circulatory biphasic regulation. First, because the drug can excite a1 receptors, high-dose, rapid administration within a short time may cause a sudden increase in blood pressure and thus lead to mental tension, restlessness, headache and a hypertensive crisis. 22 Thereafter, DEX can act highly selectively on central and peripheral a2 adrenergic receptors, reducing the concentration of norepinephrine and cortisol in the plasma and thereby inhibiting sympathetic nerves and the stress response, leading to a decrease in heart rate and blood pressure. In this current study, the patients in both groups experienced a decreased heart rate immediately after the operation (T1), which may be related to the decreased sympathetic excitability of DEX. Furthermore, the heart rate decrease in group DI was greater at T1, although the difference was not significant, which may be related to the rapid increase in the blood concentration due to the faster absorption via intravenous administration in group DI than via local administration in group DP. A previous study found that the absorption rate of DEX after intravenous administration was faster than that after local administration and the blood concentration peaked faster. 23 In contrast, when DEX was administered locally, the rate of absorption into the blood was slow, the blood concentration steadily increased and the haemodynamics were more stable. 23
The QoR-40 scale has emerged as the most widely reported indicator for evaluating the quality of postoperative recovery of patients; and is a valid, reliable and responsive measure of the QoR after anaesthesia and surgery.24,25 In this current study, compared with the scores of the patients in group DI, the global QoR-40 scores of the patients in group DP were improved; and these patients also showed certain advantages in terms of physical comfort and pain. This might be because the local administration of DEX not only leads to a certain blood concentration but also effectively increases the effect and duration of nerve blocks, reduces the pain associated with surgery and improves the quality of postoperative recovery. A previous study demonstrated that 0.5 µg/kg DEX extended the duration of analgesia of 0.5% ropivacaine by approximately 75%. 26 DEX also reduced the onset time of sensory block, with better haemodynamic stability and a higher Ramsay sedation score. 27 The current results were consistent with those of that previous study. 27 Although the use of DEX as an adjuvant to local anaesthetics could prolong the action in peripheral nerve blocks, the mechanisms are not completely understood. For ulnar nerve blocks, compared with placebo, perineural DEX prolonged the duration of sensory block by 60%, and systemic DEX administration extended it by 10%. 28 In this current study, the VAS scores were significantly lower in group DP than in group DI at 12 h and 24 h after surgery, indicating that as an adjuvant, DEX lasts longer for analgesia.
There are several reasons for postoperative nausea and vomiting in surgical patients. The combined use of opioids in general anaesthesia can aggravate the incidence of postoperative nausea and vomiting. One study showed that DEX combined with ropivacaine erector spinae plane block can provide better postoperative analgesia than DEX alone and could reduce opioid consumption, thus improving postoperative analgesia and comfort levels. 29 The cervical nerve pathway block has a definite analgesic effect, and in this current study, the incidence of nausea and vomiting in group DP was slightly lower than that in group DI, although the difference was not significant. However, it cannot be ruled out that the sample size was not sufficient to determine the difference in the incidence between the two groups. The conclusions of previous studies have in fact confirmed that the intravenous application of DEX may cause serious adverse reactions such as hypotension, bradycardia and even sinus arrest, although these occur when DEX is given at a fast rate and large doses due to dose-dependent side-effects.30,31 The concentration and speed of the DEX injection used in this current study were based on the data of previous studies,32,33 in which the data showed a relatively good blocking effect and that DEX could be safely implemented. 34 There were no serious adverse reactions in the two groups of patients in this current study.
This study had several limitations. First, it was not a multicentre study so the results cannot be generalized. Secondly, only one dose of DEX was investigated in this study. It might be possible to determine an optimal dose for patients undergoing ambulatory thyroidectomy in the future. Finally, as a secondary outcome, only the incidence of postoperative nausea and vomiting was recorded and not the severity. Future research will focus on improving the comfort for patients undergoing ambulatory thyroidectomy.
In conclusion, 0.5 μg/kg DEX combined with 0.33% ropivacaine as an adjuvant to ultrasound-guided intermediate CPB can provide better postoperative analgesia than that provided via the intravenous route, thus improving the QoR-40 score and prolonging postoperative analgesia in patients undergoing ambulatory thyroidectomy.
Research Data
sj-pdf-1-imr-10.1177_03000605231177150 - Research Data for Effect of different modes of administration of dexmedetomidine on the quality of recovery in ambulatory thyroidectomy: a randomized, controlled trial
Research Data, sj-pdf-1-imr-10.1177_03000605231177150 for Effect of different modes of administration of dexmedetomidine on the quality of recovery in ambulatory thyroidectomy: a randomized, controlled trial by Pei Gao, Wen Chen, Jin Rao, Chen Chen, Yao Lu and Yuan-Hai Li in Journal of International Medical Research
Research Data
sj-pdf-2-imr-10.1177_03000605231177150 - Research Data for Effect of different modes of administration of dexmedetomidine on the quality of recovery in ambulatory thyroidectomy: a randomized, controlled trial
Research Data, sj-pdf-2-imr-10.1177_03000605231177150 for Effect of different modes of administration of dexmedetomidine on the quality of recovery in ambulatory thyroidectomy: a randomized, controlled trial by Pei Gao, Wen Chen, Jin Rao, Chen Chen, Yao Lu and Yuan-Hai Li in Journal of International Medical Research
Footnotes
Acknowledgements
Thanks to our colleagues for their help in this study and also to the participants in this study.
Author contributions
Pei Gao, Yao Lu and Yuan-Hai Li were involved in the design of the study, data collection, data analysis, interpretation of the results, supervision of the research, drafting the original article and review of the final draft of the article. Wen Chen, Rao Jin and Chen Chen participated in the design of the study, data collection and review of the article. All authors read and approved the final draft of the article.
Declaration of conflict of interest
The authors declare that there are no conflicts of interest.
Funding
This research received no specific grant from funding agency in the public, commercial, or nor-for-profit sectors.
References
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