This single center, prospective, randomized, controlled clinical study was approved by the institutional ethics committee of National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (NCC201804009), and registered on ClinicalTrials.gov (ChiCTR1800016583). The written informed consent was obtained from every patient. Sixty-two patients with lower thoracic esophageal cancer, American Society of Anesthesiologists (ASA) physical status I and II, ages 30 to 65 years old, and selected for open thoracic surgery (Sweet procedure) were recruited in this study. All patients were able to communicate well and understood how to evaluate their pain score and total satisfaction with the anesthesia regimen. In order to eliminate potential confounders from surgeons, all open thoracic surgeries were performed by only the same experienced surgical team (Li Y, et al.). All patients were randomly allocated into the following two groups using a computer-generated random number table: group EG and group GA. In group EG, the ultrasound guided ESPB with 25 ml of 0.5% ropivacaine was performed ipsilateral before the general anesthetic induction. Then the general anesthesia was inducted. In group GA, only general anesthesia was implemented. The anesthetics scheme of general anesthesia was same in both groups. Group allocation was concealed with the use of coded, opaque, sealed envelopes. Patients with infections at the site of injection for ultrasound guided ESPB; neuropathy; coagulation disorders; morbid obesity (body mass index ≥ 40 kg/m2); allergy to ropivacaine; greater than first-degree heart block; bradycardia (heart rate < 60 bpm); pregnancy; clinically significant cardiovascular, pulmonary, hepatic or renal diseases; psychiatric illnesses that would interfere with assessment of pain score and satisfaction and those given a painkiller within one week before surgery were all excluded from this study. During preoperative interview, patients were taught how to evaluate their pain score by the numerical pain rating scale (NRS) and their own satisfaction with the anesthesia regimen by a 5-point Likert scale (5 = completely satisfied, 4 = quite satisfied, 3 = slightly dissatisfied, 2 = dissatisfied, 1 = very dissatisfied). The flowchart of this study protocol was shown in Figure 1.
Anesthesia, Monitoring, and Surgery
On arrival at the operating room, routine monitoring for open thoracotomy, including electrocardiography, invasive blood pressure, and pulse oxygen saturation (SpO2), were applied. Then a double lumen (16-gauge/16-gaunge) central venous catheter was placed by catheterization of right subclavian vein. The standardized anesthetic technique was used in the two groups. After anesthesia induction, a double-lumen endobronchial tube was placed guided by fiberoptic bronchoscopy. Then the patient was turned to a right lateral decubitus position from the supine position. The correct position of the double-lumen endobronchial tube was confirmed by fiberoptic bronchoscopy again. Before skin incision, one-lung ventilation was initiated. The volume-controlled ventilation mode was adopted, with the airway pressure and lung compliance monitored. General anesthesia was maintained with 2.5%-3.0% sevoflurane (1.3-1.5 MAC). The end-tidal carbon dioxide partial pressure was maintained between 35 to 45 mm Hg by mechanical ventilation. During the surgery procedures, 0.2 µg/kg of sufentanil was administered intravenously in both groups when the systolic arterial pressure exceeded 120% of the preoperative value or the heart rate exceeded 100 bpm. This dose was repeated every 10 minutes until the blood pressure or heart rate returned to the required limits. And rocuronium was administrated as required. The consumption of sufentanil in each group during the general anesthesia was recorded.
After ipsilateral lung collapse, a posterolateral incision in the sixth intercostals space on the left side of the chest was made to dissociate the esophagus and clear the way to access the lymph nodes in the thoracic region. The diaphragm was opened for dissociation of the stomach to clear the way for access to the abdominal lymph nodes. The anastomosis was performed at the top of the thorax using an anastomat. At the conclusion of the surgical procedure, a chest drain was placed. At the end of the surgery, sevoflurane inhalation was stopped and the intravenous analgesic pump was applied. When the reversibility of muscle relaxant was sufficient and the physiological parameters were stable, the tracheal extubation was performed. Then, the recovery time from general anesthesia and the tracheal extubation time were all recorded.
Ultrasound guided erector spinae plane block
Before the general anesthesia induction, the patient was placed in a right lateral decubitus position and a high-frequency linear ultrasound transducer (GE LOGIQe, Wauwatosa, Wisconsin) was placed in a longitudinal orientation 3 cm lateral to the T5 spinous process. Then three muscles were identified superficial to the hyperechoic transverse process shadow as follows: trapezius, rhomboid major, and erector spinae. Under the ultrasound guided, an 8-cm 22-gauge block needle (Contiplex; B Braun, Melsungen, Germany) was inserted in-plane in a caudad-to-cephalad direction until the tip lay in the surface of the transverse process (Figure 2). Correct needle tip position was confirmed by visualizing linear fluid spread that separated the erector spinae muscle from the transverse process. Then, 25 ml of 0.5% ropivacaine was injected deep to the erector spinae muscle (Figure 2). The assessment of cutaneous sensory block by pinprick was initiated 30 minutes later by a blind observer. After confirmation and assessment of the sensory block to pinprick, the general anesthesia induction was initiated.
Postanesthesia Care Unit and Postoperative Assessments
The patient was transferred to the postanesthesia care unit (PACU) after the operation. Then vital signs including heart rate, invasive blood pressure, respiratory rate, and SpO2 were monitored and recorded every 5 minutes for at least 60 minutes. A 20% decrease in systolic blood pressure from baseline was defined as hypotension. Bradycardia was a condition defined wherein the heart rate was less than 60 bpm. Hypoxemia was a condition defined wherein the SpO2 was lower than 90% at room air. Hypotension was treated by 6 mg of ephedrine and normal saline, 6 ml/kg; the same doses were repeated as required. Bradycardia was treated by intravenous blouses of 0.5 mg of atropine. And hypoxemia was treated with inhalation of pure oxygen through face mask. After the patient could communicate well at 60 minutes after surgery, the numerical pain rating scale (NRS) was used to assess patient’s pain at rest and during coughing in the PACU. 100 mg of intravenous tramadol was given as a rescue analgesic when the NRS was more than 3 at rest or during coughing. The tramadol consumption of every patient was recorded. Adverse events after the operation such as nausea, vomiting, hypotension, hypoxemia, cardiac arrhythmia, and other complications induced by drugs or puncture procedure of ESPB were all recorded and treated. The patients’ total satisfaction with anesthesia regimen was evaluated verbally at 48 hours after surgery by a 5-point Likert scale (5 = completely satisfied, 4 = quite satisfied, 3 = slightly dissatisfied, 2 = dissatisfied, 1 = very dissatisfied). All the data after surgery were recorded by an observer (W. S.J.) who was blind to the study design and group assignment.
The primary study endpoint was intraoperative sufentanil consumption. The dermatomal level of sensory block by ultrasound guided ESPB, pain score at 60 minutes after surgery, consumption of rescue analgesic tramadol, incidence of adverse events and patient satisfaction with anesthesia regimen were used as the secondary endpoint. Based on the result of previous study, excluding 0.2 µg/kg of sufentanil for induction, the average supplementary consumption of intraoperative sufentanil was 0.261 µg/kg/h for thoracic surgery. On the basis of preliminary experimental data, we calculated that a sample of 24 patients would provide 80% power at a two-sided alpha level of 0.05. Ultimately, we recruited 30 patients in each group for a total of 60 patients considering possible dropouts.
The continuous variables were presented as means ± standard deviation or median (25 th to 75 th centiles), and categorical data were presented as number and percentages. Normality was tested by the Kolmogorov-Smirnov analysis. For appropriate comparisons between the two groups, the chi-square test, Student t-test, Mann-Whitney U-test, or Fisher exact test was used if needed. All data were processed by IBM SPSS Statistics 21.0 (IBM Inc., New York, NY). A 2-sided p value less than 0.05 was considered to be statistically significant.