2.1 Study design:
This is a prospective, randomized and controlled clinical trial . The study was carried out in the First Affiliated Hospital of Bengbu Medical College. The ethics was approved by The Ethic Committee of the First Affiliated Hospital of Bengbu Medical College(approval number:
2021KY063). The trail was registered in Chinese Clinical Trial Registry system on 21 November 2021 , registration number was ChiCTR2100053449 . The participants were involved from November 22, 2021 to March 20, 2022.
100 elderly patients with lung cancer who underwent thoracoscopic surgery in the First Affiliated Hospital of Bengbu Medical College were randomly divided into SGB group and control group. The Inclusion criteria include the following:(1)Age 60-80; (2)BMI between 20-27.9kg/m2 ; (3)American Society of Anaesthesiologists (ASA) physical status I-III. The exclusion criteria include the following: (1)Inability to cooperate; (2)history of thoracic operation; (3)coagulopathy; (4)the operation transfer to thoracotomy; (5) postoperative VAS(Visual Analogu Scale) score≥4; (6)allergy to ropivacaine; (7)Liver and kidney dysfunction; (8)Bradycardia or arrhythmias; (9)Sleep apnea syndrome. (10)Serious complications:cerebral infarction ,cerebral hemorrhage or heart failure and so on.
2.3 Randomization and blinding
92 eligible patients were randomly assigned to the stellate ganglion block group (SGB group) or the control group in a 1:1 ratio. The randomization sequence was generated by an uninvolved teacher (Dr. Zhu) using SPSS package (version 25; IBM Corp, Armonk, NY, USA), and the group allocation were sealed by Dr. Zhu in identical, opaque and sequentially numbered envelopes. Envelopes were opened and revealed the allocation group when eligible patients are available in the pre-operative room. An experienced anesthesiologist (Dr. Wei) who was not involved to the study performed ultrasound-guided the stellate ganglion scanning or blocking at the C6-7 level in the pre-operative room, After that, another anesthesiologist who was not involved in the study performs routine induction and maintenance of anesthesia. All patients and data collectors were blinded.
2.4 Clinical Interventions
Once eligible patients entering to the pre-operative room, venous blood was collected 5 ml to vessels with heparin sodium after intravenous access was accessed in the pre-operative room. Dr. Wei performed the stellate ganglion scanning or blocking under the ultrasound guidance at the surgical side according to the grouping allocation after the peripheral intravenous access was secured. In supine position, patients’ neck was slightly extended.The anatomy of C7 level (C7 with only one posterior tubercle) and C6 (C6 with two tubercle) level were found under the high-frequency linear array ultrasound probe with imaging depth of 4cm. At the level between C6- 7, the following anatomical structures were found under the ultrasound guidance:The common carotid artery, internal jugular vein, longus colli muscle and prevertebral fascia. The stellate ganglion located on the surface of longus colli muscle and deep prevertebral fascia.In SGB group, 7ml 0.5% ropivacaine were injected when the tip of 22-gauge needle to the stellate ganglion site in-plane approach under ultrasound guidance. After observing 20 minutes, the appearance of Horner syndrome meant that the SGB was successful.
In operating room, monitoring included BIS, electrocardiography, heart rate (HR), systolic blood pressure (SP), diastolic blood pressure (DP), pulse oxygen saturation.General anesthesia induction drugs included:propofol1- 2mg/kg , sufentanil 0.5ug/kg , cis-atracuride 0.2mg/kg. 3 minutes later, the double-lumen tracheal catheter was inserted, and the correct position was adjusted through the fiber-optic bronchoscopy. Half an hour after induction, all patients were routinely given 5mg tropisetron was to prevent postoperative nausea and vomiting. The respiratory parameters was adjusted to maintain end-tidal carbon dioxide at 35-45mmHg. Anesthesia maintenance included propofol 2-3mg/kg/h, remifentanil 0.3ug/kg/min, inhalation oxygen flow 2L /min, sevoflurane 1.5%. Cis-atracuride was administered every 40-60 minutes, 10ug sufentanil was administered by 30 minutes before the end of surgery. During the operation, the BIS value was maintained at 45-60 by adjusting the infusion rate of propofol. norepinephrine and nitroglycerin were used to maintain fluctuation of blood pressure within 20% of baseline during the operation. After surgery, the patient was transferred to PACU for further observation until the patient was awake to extubation. After that, the patient was sent to the lintensive care unit of the thoracic surgery department.
Postoperative analgesia management
Postoperative analgesia pump was used in all patients to relieved pain, all patients used the same patient-controlled analgesia (PCA) . 100ug sufentanil and 10mg tropisetron diluted to 100ml in PCA.The program of the PCA system included:The bolus dose of 2mL, continuous infusion speed was 2mL /h , the single dose was 2mL, and the locking time was 30min. All patients and their families knew how to use PCA.
2.5 The study outcome：
The primary outcome were sleep duration and the sleep efficiency index which were measured by BIS-Vista monitor. When the values of BIS ≤80, it means entering to the sleep state, and the values of BIS ≤40, it means entering the N3 sleep stage.9 Sleep duration was defined as the duration of BIS ≤80 within 8 hours of monitoring time (22:00-06:00); The sleep efficiency index means that the ratio of total sleep time to the monitored 8 hours.10 BIS-Vista monitor was used to monitor the sleep of patients on the last night before surgery (seep1), the first nights after surgery (sleep2) and the second nights after surgery (sleep3)（from22:00-06:00). The secondary outcomes including: N3 stage of sleep on the last night before surgery(N3-1), the first night (N3-2) and the second night(N3-3) after surgery ,the Athens Insomnia Scale (AIS) score on the last night before surgery(AIS1), the first night (AIS2) and the second night(AIS3); the concentration of 6-hydroxysulfate melatonin (6-HMs) in urina sanguinis; the concentration of norepinephrine and cortisol in plasma; pressing the analgesic pump times within 48 hours after surgery; Visual Analogu Scale (VAS) score at 10pm of the first(VAS1) and second(VAS2) night after surgery;VAS score on the first walk after surgery.
2.7 Measurement of the stress response index and sleep hormone
5ml of venous blood was taken into a vacuum tube with heparin sodium at the following time points: before anesthesia (T1),5min after extubation (T2), at 6am on the first morning after surgery(T4). 3ml urina sanguinis into vacuum tube was collected at the following time points: at 6am in the morning of surgery(T3), at 6am on the first morning after surgery(T4), at 6am on the second morning after surgery(T5). Then the specimen was centrifuged at 3000 RPM for 30min, and the supernatant was stored in a refrigerator at -80℃. Biochemical markers of stress in plasma include norepinephrine and cortisol. The metabolite of sleep endocrine hormone - melatonin is 6-hydroxysulfate melatonin. Measurement of 6-hydroxysulfate melatonin in urine can reflect the secretion of melatonin at night. 11Norepinephrine, cortisol and 6-hydroxysulfate melatonin were measured by enzyme-linked immunosorbent assay (ELISA).
2.8 Sample size
According to the sleep duration(mean ± standard deviation [SD]) on the first postoperative night in our Preliminary experiments(the SGB group:212.33± 125.366 min; the control group: 124.86 ±126.069 min), the sample size was 34 patients in each group with assuming a two-sidedαof 0.05 and a power of 0.80 by using https://www.cnstat.org/samplesize/7/. Considering some patients could be drop-out during the follow-up visits, we need to acquire 100 patients in each group.
2.9 Statistical analysis
SPSS(Version 25; IBM Corp, Armonk, NY, USA) software was used for statistical analysis.The categorical data were presented as percentage or frequency, and were analyzed by Chi-square test or Fisher’s exact test.Continuous data were presented as mean ±SD or median [25% percentile, 75% percentile], then used Kolmogorov-smirnov test to analyze whether the data had the normal distribution or not.The normal distribution data were analyzed by independent T test and the non-normal distribution data were analyzed Mann-Whitney U-test. It was considered as Significant difference when P value < 0.05.