This single-center, single-blinded, prospective, randomized study was approved by the Institutional Review Board and Hospital Research Ethics Committee of the Second Affiliated Hospital of Anhui Medical University [No. PJ-YX2018-004 (F2)]. The protocol of the study was registered in the Chinese Clinical Trial Registry (No. ChiCTR1800016429) and executed in accordance with the CONSORT checklist. Each patient provided written informed consent before participation in the study. Patients can withdraw from the study at any time according to their wishes. All patients were enrolled between June 2018 and April 2019. The inclusion criteria were as follows: male patients aged 18-70 years and American Society of Anesthesiologists (ASA) physical status I-II undergoing elective surgery, scheduled general anesthesia, and intraoperative catheter insertion. The exclusion criteria were as follows: urology patients, end-stage renal disease, pathological obesity, central nervous system dysfunction, chronic pain, cerebral infarction, mental disorder of consciousness, change in surgical and anesthesia plans, without CRBD when admitted to PACU. In this single-blinded study, patients were blinded to the group allocation. However, it was not blinded to anesthesiologists, PACU nurses, surgeons and ward nurses because this information is important for perioperative management of patients.
PASS 11.0 software was used to compare the mean of two independent samples. According to the pre-experiment CRBD score, the mean value of the control group was 2.25, and the standard deviation was 0.66. The mean value of the dexmedetomidine group was 1.9 and the standard deviation was 0.67. Set α as 0.05, β as 0.9, using bilateral test，the sample size of each group is 75. Increase the sample size 20% to prevent the sample drop-out, so we chose 90 patients in each group.
Male patients with CRBD into PACU were randomly divided into two groups with an allocation ratio of 1:1 according to the computerized randomization table in a blinded manner. Random numbers to each patient while the nurses collected postoperative data from the patients.
The surgery and anesthesia program of the patient was similar to that of the other patients. Electrocardiography (ECG), peripheral oxygen saturation (SpO2), non-invasive blood pressure (NBP), and respiratory rate (RR) were monitored routinely after the patients were admitted to the operating room. The vein channel was established with a 22-gauge indwelling needle. Oxygen was inhaled by mask (oxygen flow rate was 4-5 L/min). Midazolam 0.025 mg/kg, sufentanil 2-4 μg/kg, etomidate 1-2 mg/kg, and rocuronium 0.9 mg/kg were injected intravenously for anesthesia induction. After intubation, a ureteral catheter was used for catheterization, followed by anesthesia maintenance propofol 2-4 mg/kg/h, remifentanil 10-20 μg/kg/h, and continued addition of cisatracurium to maintain muscle relaxation. At the end of the operation, the muscle relaxation and consciousness of the patient were restored, the tracheal tube was removed and sent to PACU for observation.
After induction of anesthesia, 16F latex ureteral catheter (Huaxing Medical Equipment Co., Ltd, China) was used for all participants. Catheterization was performed by surgeons with more than 5 years experience. The operation process must be as gentle as possible, and the whole process was sterile. Before catheterization, paraffin oil fully lubricated the catheter. After the successful placement of the catheter, 10 mL of normal saline was injected into the cuff balloon to prevent catheter slippage. After catheterization, the catheter was fixed on the inside of the thigh to prevent urinary tract injury caused by catheter pulling.
As a safe and widely used drug, intravesical dexmedetomidine instillation method has been approved by the Institutional Review Board and Hospital Research Ethics Committee of the Second Affiliated Hospital of Anhui Medical University. In the dexmedetomidine group, 0.5 μg/kg dexmedetomidine was solubilized in 20 mL normal saline infused from the ureteral catheter to bladder for intravesical dexmedetomidine instillation. In the control group, 20 mL of normal saline was infused from the ureteral catheter to the bladder. After instillation, the ureteral catheter was clipped for 30 min and then unclipped.
The primary outcome endpoint was CRBD grade, and the second outcome endpoint was urethra pain NRS score and patient's satisfaction. The duration of anesthesia, the time length of operation, the time from the end of the operation to full consciousness, and patient characteristics were recorded. Mean arterial pressure (MAP), heart rate (HR), RR, SpO2, CRBD grade, and urethra pain NRS score were recorded when the patient was sent to PACU (T0) , the time of intravesical instillation with dexmedetomidine or normal saline (T1), 30 min after intravesical instillation (T2), 1 h after intravesical instillation (T3), 2 h after intravesical instillation (T4), the time point of leaving PACU (T5), 6 h after operation (T6), and 24 h after opertaion (T7). The NRS score of urethra pain and the complications after intravesical instillation were also recorded. The patient satisfaction score were recorded when leaving PACU and 24 h after the operation. The NRS score was used for the assessment of urethra pain in both groups. CRBD grade: grade 0, patients have no discomfort at all; grade 1, patients have slight discomfort, only when asked to show discomfort; grade 2, patients have moderate discomfort, frequency of urination, the urgency of urination, feeling of lower abdominal distension, which is not easy to bear; grade; 3, the patient had severe discomfort, intolerable distension, urethral pain, frequent urination with strong restlessness, and needed to be removed. Ramsay score: 1 point, the patient is restless and fidgety; 2 points, the patient is quiet and cooperative; 3 points, the patient is sleepy and can follow the instructions; 4 points, the patient is in a sleep state and can wake up; 5 points, the respiratory response of the patient is slow; 6 points, the patient is deep asleep and has no response to stimulation. Patient satisfaction score is consisting of integers from 1 point to 5 points: 1 point means dissatisfied and 5 points mean very satisfied. The urethra pain NRS scores consists of integers from 0-10 points; 0 point means no urethra pain, and 10 points indicate intense urethra pain. Subsequently, the patients selected an integer to describe the intensity of their urethra pain while using a ureteral catheter.
SPSS software (version 22.0, Chicago, USA) was used for statistical analysis. The age, weight, blood, and other measurement data of patients were presented as mean ± standard deviation. The ASA classification data were expressed as counts. Student’s t-test or the Mann-Whitney U test was used for continuous variables, such as age and weight. The c2 or Fisher’s exact tests were assessed for categorical variables, such as ASA grade and patient satisfaction score. ANOVA was used for the comparison of MAP, HR, SpO2, and other data at different time points. p-value <0.05 was accepted as statistically significant.