The randomized clinical two-arm parallel study has been approved by the Medical Ethics Committee of the second hospital of Anhui medical university, Hefei, China (Approval No: PJ2016-019-01). All patients signed written informed consent forms prior to their participation in the study protocol. The trial was registered before patient enrollment at the Chinese Clinical Trial Registry (ChiCTR1900024303; principal investigator：Ye Zhang; date of registration, July 5th, 2019).
Participants and randomization
A total of 80 patients aged 65–85 years underwent hip arthroplasty admitted to the Second Affiliated Hospital of Anhui Medical University between July 2019 and September 2019 were included in this study (Figure 1). The inclusion criteria were the following：all were classified as class II or III according to the American Society of Anesthesiologists (ASA) physical status and had no history of mental illness, neurological disease, severe heart, lung, liver, or kidney disease, or evident thoracic or spinal deformity. Exclusion criteria were：serious respiratory or circulatory diseases, such as severe atherosclerosis of coronary artery, arrhythmia, cardiac valve pathologies, arteriosclerosis, cardiac pacemaker, automated implantable cardioverter defibrillator, cardiac failure, chronic obstructive pulmonary disease and obvious liver or kidney dysfunction.
A computer-based list was generated (www.random.org), and subjects were randomly assigned (sequence number use, opaque, sealed envelopes) to a set of two groups: VCV group (V-group) and SIMV group (S-group). Written informed consent was obtained before the recruitment of subjects in the study. Researchers not involved in the treatment of perioperative assessment of outcome variables, and group assignments and intervention knowledge.Intervention
The patient examination included peripheral venous access, blood pressure (BP) measurement, electrocardiogram (ECG), oxygen saturation (SpO2), and sedation depth—bispectral index (BIS). In addition, radial artery catheterization was performed under local anesthesia to monitor the invasive arterial pressure of the patients. Prior to the induction of anesthesia, each patient was administered 20 ml of 0.375% ropivacaine under the guidance of ultrasound or neurostimulator in order to block the lumbar plexus block, sacral plexus, or both. The blocking effect was confirmed. Anesthesia was achieved using 8% sevoflurane for tidal volume induction. Once the patients lost consciousness, 0.15 mg/kg cis-atracurium was administered via intravenous bolus injection. When the sedation depth value fell below 60, the laryngeal mask airway (LMA) was placed, followed by connection to a Mindray anesthesia machine for controlled ventilation. The parameter settings were as follows: The ventilation was set to tidal volume 8 ml/kg, the respiratory frequency ranged from 10 to 15 times/min, the inspiratory/expiratory phase ratio was 1:2, the pressure limit was 30 cm H2O, the inhaled oxygen concentration reached 60%, and the flow rate was 2 l/min. The end-tidal CO2 pressure（PETCO2） ranged from 30 to 40 mmHg. To maintain anesthesia, sevoflurane inhalation and intravenous dexmedetomidine were provided according to the BIS value (maintained between 60 and 70). These anesthetics were used to monitor the depth of general anesthesia, and their doses were adjusted accordingly. The hemodynamic stability of each patient was maintained. In the case that the mean arterial pressure was reduced to more than 30% compared with that of the basal value, 40 µg phenylephrine was administered intravenously. In the case that the mean arterial pressure was increased to more than 30%, 10 mg urapidil was administered intravenously.
Dexmedetomidine was discontinued 30 min prior to the end of surgery, and sevoflurane was discontinued and flushed out 10 min prior to the end of surgery. The muscle relaxation was antagonized with neostigmine and atropine. The tracheal tube was removed from each patient once he or she had recovered from anesthesia and achieved the extubation indications. The extubation indications were as follows: the patient was awake, could follow instructions, and met the criteria of 14–20 spontaneous breaths per min, 10 min air intake, SpO2 >92%, and PETCO2<45 mmHg. A patient-controlled intravenous analgesia (PCIA) pump was applied postoperatively for analgesia (3 µg/kg sufentanil + 3 mg granistron pre-diluted in 100 ml normal saline) at a loading dose of 2 ml, a background dose of 2 ml/h, a single dose of 2 ml, a 15 min locking time, and 48 h analgesia to keep the postoperative visual analog scale (VAS) score for pain ≤3.
The primary endpoint was pulmonary function. A PONY FX spirometer (COSMED, Italy) was used for pulmonary function monitoring of forced vital capacity (FVC), forced expiratory volume (FEV) during the first second, and maximal voluntary ventilation (MVV) at the following times: upon entering the operating room (T0), at postoperative day 1 (T1), at postoperative day 3 (T2), and at postoperative day 5 (T3). At each time point, three measurements were obtained and the largest value was recorded.
The second endpoints included airway pressure, arterial blood analysis, pulmonary infection and duration of hospitalization. The peak airway pressure was measured at 5 min, 0.5 h, and 1 h following the insertion of LMA. A GEM Premier 3500 blood gas analyzer (Werfen Instrumentation Laboratory, San Diego, CA, US) was used for blood gas analysis of arterial blood samples collected at the following time points (oxygen inhalation temporarily stopped 30 min prior to blood collection) as follows: prior to anesthesia induction (T0), prior to extubation (T1), at the time of exit from the anesthesia intensive care unit (AICU) (T2), and at postoperative day 1 (T3). The patient clinical pulmonary infection scores (CPIS) were reviewed on postoperative day 1 (T1), postoperative day 3 (T2), and postoperative day 5 (T3) to evaluate pulmonary infections. The duration of hospitalization of each patient was also recorded. All results were recorded by researchers that were not familiar with the group allocation.
The sample size calculation based on the preliminary trial results of postoperative pulmonary function. We aimed to detect the postoperative value of FVC in the SIMV group was 5% higher than that of the VCV group with a power of 80% and a two-sided significance level of 5%, the calculated sample size was 29 subjects per group.
In the present study, the SPSS 17.0 software (IBM SPSS Inc., Chicago, IL, US) was used for statistical analysis. Normally distributed measurement data were presented as mean ± standard deviation (i±s). Measurement data from a randomized block design were compared using the student’s t-test. Measurement data of repeated measurement design were compared using the repeated measures ANOVA. Categorical variables were compared using the chi-squared test. A P value lower than 0.05 (P<0.05) was considered statistically significant.