Patients
After taking institutional ethics committee (The second affiliated hospital, The Third Military Medical University, Chongqing, China) approval, the trial was registered after patient enrollment at Chinese Clinical Trial Registry,
http://www.chictr.org.cn/listbycreater.aspx (ChiCTR1800014282c, January 3, 2018). Written informed consent was obtained from all enrolled patients. From December 2017 to March 2018, a total of 142 patients who were scheduled for elective thoracic surgery, aged 20 to 65 years, with American Society of Anesthesiologists (ASA) physical status I or II were recruited. Exclusion criteria included history of severe heart, hepatic or renal disease, pre-existing of lung disease (chronic obstructive pulmonary disease with forced expiratory volume in one second of predicted and/or over forced vital capacity ratio less than 0.8 and/or 0.7 respectively, pneumonia or atelectasis), preoperative respiratory failure (PO
2<60 mmHg or PCO
2>50 mmHg), allergy to the studied drugs, and history of chronic pain condition or opioid use.
Anesthetic procedure
Monitoring of patients during the surgery was accomplished by electrocardiogram (ECG), pulse oximetry (SpO
2), the radial artery catheter placement, mean arterial pressure (MAP), end-tidal carbon dioxide (
ETCO
2) and bispectralindex (BIS). General anesthesia was induced by intravenous injection with midazolam (0.1 mg/kg), atracurium (0.15 mg/kg), propofol (2-3 mg/kg), sufentanil (0.4 μg/kg), and tracheal intubation with a double-lumen tube of appropriate size. Anesthesia was maintained with sevoflurane(1–2%), propofol(6-8 mg/kg/h), remifentanil(0.5-1 μg/kg/min), and atracurium as necessary. Patients were mechanically ventilated with 8 ml/kg during two lung ventilations, reduced to 5 ml/kg with 5 cmH
2O PEEP during one-lung ventilation and the frequency was adjusted to keep the end tidal carbon dioxide (ETCO
2) between 35 and 45 mmHg [
15]. The inspired oxygen fraction (FiO
2) was increased if necessary to maintain oxygen saturations (SPO
2) greater than 90%. Alveolar recruitment strategy: the PEEP was increased from 5 cmH
2O to 40 cmH
2O by a level of 5 cmH
2O at a ventilatory frequency of 8 bpm with a tidal volume of 7–8 ml/kg until the alveolar recruited, and then reduced to previous 5 cmH
2O gradually [
16].
For all included patients, operations were done by the same experienced surgeons. After the end of the skin closure, all patients were given sufentanil (0.1 μg/kg), Ramosetron (0.3 mg), and if patients reported the pain-NRS ≥ 4, followed by 5 mg boluses dezocine.
Postoperative pain management.
Mechanical intravenous analgesia pump (200 mL, Beijing KSH Technology Institute, Beijing, China) was used and parameters were set as background dose 4 ml/h, PCA dose 1 ml, locking time 15 min. In the hydromorphone (HUMANWELL HEALTHCARE, Hubei, China) group (group A) PCA with a mixture of hydromorphone (0.2 mg/kg), dezocine (0.5 mg/kg, Yangtze River Pharmaceutical, China), and ramosetron 0.6 mg was applied. While in sufentanil (HUMANWELL HEALTHCARE, Hubei, China) group (group B) PCA with a compound of sufentanil (3.0μg/kg), dezocine (0.5 mg/kg), and ramosetron (0.6 mg) was used. During the PCA treatment, when inadequate analgesia presented, rescue analgesia was given suing dezocine 5 mg.
Outcomes.
PPCs evaluation was performed by an independent and experienced surgeon after surgery at the same time each day up to discharge. Using the Melbourne Group Scale (MGS), PPCs was defined in those patients presenting with four or more of the following eight dichotomous factors: temperature>38 °C; white cell count>11.2 × 10
9/L; chest X-ray findings of atelectasis or consolidation; signs of infection on sputum microbiology; purulent sputum; physician diagnosis of pneumonia; SPO2<90% on air; and prolonged intensive care (ICU) or hospital stay [
17]. Respiratory failure was defined according to artery gas analysis (PO
2<60 mmHg or PCO
2>50 mmHg) when patients respired air [
18].
Rest pain NRS was considered as the secondary outcome. In addition, demographic data including age, weight, smoking index (the number of cigarettes smoked per day multiply by number of years of smoking) [
19], and artery blood gas analysis were recorded before operation. Intraoperatively, duration of surgery, total dose of remifentanil and sufentanil were recorded. Pain NRS (0, no pain to 10, worst pain), Ramsay sedation score (1, anxious, agitated, or restless; 2, cooperative, oriented, and tranquil; 3, response to command; 4, brisk response; 5, a sluggish response; 6, no response) and nausea or vomiting score (0, without nausea or vomiting; 1, mild; 2, middle; 3, serious) were collected at 0 h, 6 h, 12 h, 24 h, 48 h after extubation [
20]. The skin pruritus was divided as mild, middle and server. CRP (C-reaction protein), inflammatory cells and blood gas analysis at 12 h after operation were also measured. And length of ICU and postoperative stay was recorded.
Statistical analysis
The primary outcome of the current study was the incidence of PPCs. Previously published data have showed that the incidence of PPCs was 28% [
21]. On the basis of preliminary experimental data, we hypothesized hydromorphone may reduce the odds of pulmonary complications to 15%. Under these conditions, 56 patients per group were required to reach a power of 80% (one-side hypothesis) and a 0.05 risk of type I error. Thus, considering about 20% loss of follow-up, we decided to include 71 evaluable patients for each group.
Date were presented as number, percentages, median (range) or mean ± SD and analyzed using the SPSS 19.0 software. Chi-square test was used to compare the difference of categorical data between two groups. The difference of pain NRS between two groups was compared by the use of two independent samples nonparametric test (the Mann-Whitney test). Independent samples t-test was used to compare the continuous variable data between 2 groups. Two side P-value < 0.05 was considered to be statistically significant.