Study design, setting, population, and data collection
This single center retrospective cohort study was conducted at a teaching hospital in China with 1500 beds. The Ethics Committee approved this study. This study extracted data get from the database.1 This study analyzed data from adults patients (age ≥ 18 years old) who underwent elective thoracic and abdominal surgery between January 1, 2013, and December 31, 2018. The procedures that were included in the present study were abdominal or thoracic surgery because these involve both epidural and PNB techniques. In the current study, we only included information from the first procedure for patients operated on more than twice within one year. If one patient received two surgeries in separate years, two surgeries were counted. Cardiac, obstetric, or emergency surgery was also excluded from the present study. Additionally, estimated preoperative glomerular filtration rate of less than 60 mL/min/1.73 m2, preoperative serum creatinine (sCr) levels greater than 176 μmol/L, or a previous history of renal dysfunction were also excluded from the present study.
Exposures of cohorts
The exposure of cohorts in this study was different regional blockade techniques (peripheral nerve blockade versus neuraxial epidural) under general anesthesia.
In the operation room, standard monitoring was carried out, including electrocardiogram (ECG), SpO2, non-invasive or invasive blood pressure, end tidal CO2, and body temperature. In patients receiving surgeries under general anesthesia, intravenous propofol (1–3 mL/kg) or Etomidate (0.2-0.6 mg/kg) with rocuronium (0.6–1.0 mg/kg) or cis-atracurium (0.1–0.2 mg/kg) and sufentanil at induction (0.25-1ug/Kg) was used for induction. After induction, Patients with inhalation anesthesia was maintained with 1–1.5 minimum alveolar concentration of inhalational agents (sevoﬂurane) with or without 50% nitrous oxide. After the procedure was completed, the inhalation agent and nitrous oxide were turned oﬀ and the lung was ventilated with 100% oxygen. Patients with total intravenous anesthesia (TIVA) were infused with propofol (1%,20-40 ml/h), intraoperative analgesic included sufentanil (5-10 ug/time or TCI 0.1-0.3 ng/ml) or remifentanil (TCI 2-3 ng/ml) were used for maintaining. The fresh gas flow rate was kept constant at 2-3 L/min, and minute ventilation was regulated based on ETCO2. The tidal volume and respiratory rate were set at 6–8 mL/kg and 10–12/min, without positive end-expiratory pressure (PEEP). In patients with decreased SpO2, 5 cm H2O PEEP was applied. When an attempt of self-respiration appeared, a cholinesterase inhibitor with anticholinergics was administered and extubation was performed. Self-controlled post-operative analgesic infusion pump (sufentanil 1-1.5ug/ml, bollus at 2ml, lock time 8-10 min) was used when necessary or patient requested. Blood pressure was kept within a normal range in both groups. If systolic blood pressure dropped below 90 mmHg or 30% from baseline, ephedrine (3–12 mg) or phenylephrine (50–100 µg) was injected. In the case of persistent hypotension, continuous infusion of phenylephrine or non-adrenaline was administered. When the blood pressure was high despite the adequate anesthetic depth and suﬃcient analgesia, calcium channel blocker or beta blocker was administered considering the underlying disease of the patients and other vital signs upon the decision-making of a staﬀ anesthesiologist. When severe bradycardia (HR < 45 BPM/min) was observed, atropine (0.2 mg) was applied. Calculating the maintenance volume and bleeding, as well as the patient's volume status, crystalloid and colloid solution was infused. Blood transfusion was carried out based on the amount of hemorrhage and the hematocrit level.
Regional blockade techniques
PNB consisted of 0.375 – 0.5% ropivacaine 10-40 ml after needle head satisfiedly reached target zone with ultrasound guidance. Epidural was performed at the lateral decubitus position, a loss of resistance technique was used for identification. A plastic tube was inserted into the epidural space, and continuous or intermittent 0.375 – 0.5% ropivacaine or 1% lidocaine was injected.
Variables used in the present study
This study retrospectively extracted demographic, surgical, preoperative disorders, Intraoperative variables and outcome data of all patients from the perioperative database. The demographic data included age, sex, body mass index (BMI), smoking and alcohol habits. Surgical data included the operator, The modified John Hopkins Hospital criteria (MJHSC), whether or not intraperitoneal surgery. Preoperative disorders data included medical history, including the presence of hypertension, coronary artery disease, cerebrovascular disease, diabetes, pulmonary disease, adrenal insufficiency, and the use of the following medications: angiotensin converting enzyme inhibitor/angiotensin receptor blocker, beta blocker, calcium channel blocker, antiplatelet agent, HMG-CoA reductase inhibitors, non-steroidal anti-inflammatory drugs (NSAIDS), selective COX-2 inhibitor, other analgesics, and steroids. In addition, preoperative laboratory findings, including anemia, platelet, white blood cells, blood sodium level, C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, uric acid and creatinine, as well as transthoracic echocardiographic, were also documented. Intraoperative variables including the use of vasopressor, calcium channel blocker, and beta blocker, the total volume of infused crystalloid and colloid, intraoperative packed red blood cell transfusion, and the intraoperative hypotension, lowest mean blood pressure (MBP), hypoxemia, level of end-tidal CO2, mean heart rate were evaluated. In addition, the operation and anesthesia time were also calculated.
The primary outcome of this study was the association of the anesthetic technique with the occurrence of AKI in patients following thoracic and abdominal surgeries. AKI was defined based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria defined as postoperative serum creatinine level increase to no less than 26.5 μmol/l within 48 hours, or 1.5 times from the baseline 7 days after surgery, or initialization of blood dialysis.2-8
Secondary outcome variables were classified postoperatively as follows: cardiovascular complications: composed of Acute myocardial infarction (STEMIs & NSTEMIs), new congestive heart failure, non-fatal cardiac arrest and death within 7 days postoperatively.9-12
Patients were divided into two cohorts according to the anesthetic technique that was used on them. Continuous variables with a normal or non-normal distribution were compared using the Student t-test or Mann-Whitney U-test, respectively. The Kolmogorov-Smirnov test was used to determine whether the data was normally distributed. Categorical variables were compared by the Chi-Square test or the continuity-corrected Chi-Square test or exact Fishers’ test. Rank variables were compared using the Kruskal-Wallis H-test. Statistical significance was defined by a two-tailed P < 0.05.
Multivariate logistic regression to detect anyassociation between theanesthetic techniqueand AKI
A logistic regression model was constructed, and confounders were assessed based on a priori knowledge and other studies.2-8,13,14 The following covariates were considered: AKI risk index, which defined as: age 56 years old or older, male sex, emergency surgery, intraperitoneal surgery, diabetes mellitus necessitating oral therapy, diabetes mellitus necessitating insulin therapy, active congestive heart failure, ascites, hypertension, mild preoperative renal insufficiency, and moderate preoperative renal insufficiency. Other variables included preoperative hemoglobin, creatinine and albumin, cancer surgery, surgical complexity (Modified John Hopkins hospital criteria, MJHSC 11), intraoperative hypotension, intraoperative blood transfusion,intraoperative colloid use. Multicollinearity among these variables was assessed by the variance inflation factor, with a reference value of 2. le Cessie - van Houwelingen - Copas - Hosmer unweighted sum of squares test was used for the goodness of fit. Discrimination of the multivariate model was assessed based on the c-statistic. A heterogeneity analysis was used to determine if there were any differences in the treatments' effects between the different subgroups defined by covariates included in the model. The adjusted odds ratio for AKI in both subgroup was calculated, and the interaction effect of covariates was tested for the relationship between anesthesia type and outcomes. Sensitivity logistic regression models were constructed as following: (i) adjusting for the duration of the surgery.
Analysis of the propensity score matching
To reduce the inﬂuence of potential confounding factors, Propensity score (PS) matching analysis was performed to modify intergroup diﬀerences according to the anesthetic technique. Table 2 shows demographic and perioperative variables used for estimating the PS. Using greedy matching algorithms, this study used a caliper of 0.25 SD of the logit of the PS to match patients at a ratio of 1:1. Logistic Model discrimination and model calibration were evaluated with c statistics (0.729) and le Cessie - van Houwelingen - Copas - Hosmer unweighted sum of squares test (p = 0.224). This study evaluated the balancing in demographic, surgical, and preoperative covariates of the PS-matched cohort by the standardized mean diﬀerence. All absolute standardized diﬀerences after PS were less than 10%. The risk of outcome variables, including occurrence of morbidity, were re-analyzed by logistic regression in the total and PS-matched cohort. Statistically signiﬁcance was set at p < 0.05.
All data management and statistical analysis were performed using the R programming language (v.3.6.2).