This article is reported as per Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines (www.consort-statement.org) (Supplementary Material Table S1).
This study is a follow-up to our previous study. We conducted an explorative post-hoc analysis of our previous single-center, randomized, sham-controlled clinical trial . As already described elsewhere , this study was conducted in a high-volume center for thoracic aortic surgery from April 2017 to March 2018. The Ethics Committee of Fuwai Hospital approved the study (No. 2016–835). All participants provided written informed consent before randomization. The clinical trial was registered at clinicaltrials.gov before patient enrollment ((NCT03141385). All procedures were conducted in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments.
In our previous study, one hundred thirty participants who underwent open total aortic arch replacement were randomly assigned in a 1:1 ratio to undergo either RIPC or sham RIPC (control group).Randomization, treatment assignment, and implementation of two interventions by clinical researchers who are not involved in data collection and analysis.
Procedures and Interventions
This procedure was performed to treat extensive aortic dissections or aneurysms and replace the arch using a tetrafurcate graft with stented elephant trunk implantation. All procedures were performed through a standard median sternotomy under cardiopulmonary bypass (CPB). After induced anesthesia, RIPC and sham RIPC were conducted before skin incision. In the RIPC group, four cycles of 5-min inflation at 200 mmHg or at least 50 mmHg higher than systolic pressure in the right upper limb were performed, and 5-min reperfusion with the cuff deflation was subsequently conducted. In the sham group, sham RIPC was performed, comprising four cycles of pseudo-ischemia and reperfusion (5-min blood pressure cuff inflation at 20 mmHg) in the right upper limb and a subsequent 5-min cuff deflation.
Surgeons in our clinical center routinely advise patients return to the hospital for 3 months of follow-up after surgery to observe whether the patients recover well. Eighty percent of patients in our study came to our clinical center for 3 months of postoperative follow, which was conducted with related blood biochemical examination and imaging examination. Thus, the data of eighty percent of patients were obtained from hospital records, and the data of the other twenty percent of patients were obtained by phone interviews with patients and family members 90 days after surgery. A variation of ±3 days was allowed for logistical reasons.
AKI is a serious postoperative complication, but CKD is even more severe. In order to observe the renal status of patients after AKI, a common indicator of general acceptance and chronic renal insufficiency must be established. Emerging demand for dialysis following AKI and persistent renal dysfunction (worsened CKD) after AKI herald subsequent possible major morbidity and death. In addition, considering that death after AKI is actually more common than dialysis and is the ultimate major morbid outcome after AKI, its inclusion in a composite endpoint is practically mandatory . Thus, the composite outcome of death, new dialysis, and persistent renal dysfunction constitutes MAKE . MAKE should be assessed at specific time intervals following AKI diagnosis, of which 90 days may be the best endpoint because that is typically the threshold when CKD is diagnosed after AKI .
The key endpoint of this study was the composite outcome MAKE consisting of all-cause mortality, persistent renal dysfunction and dialysis in all patients within 90 days postoperatively. The secondary endpoints were all-cause mortality, persistent renal dysfunction and dialysis in all patients within 90 days postoperatively. Other secondary endpoints included the composite outcome MAKE in patients who developed AKI after open total aortic arch replacement within 90 days postoperatively.
Specifically, the definition of clinical endpoints of the Zarbock et al. study have been used for reference for our study, because the study also examined the 90-day impacts of RIPC on kidney function in patients at high AKI risk (Cleveland Clinic score ≥ 6) undergoing cardiac surgery. The definition of persistent renal dysfunction was serum creatinine levels greater than or equal to 0.5 mg/dl (44 μmol/L) over baseline serum creatinine in patients not receiving dialysis or dialysis dependency . Patients who died within 90 days could not be assessed for persistent renal dysfunction or dialysis.
Statistical Analysis of the Data
The key endpoint of and the secondary endpoints in this study were examined using a 2-sided Pearson’s χ2 test or Fisher’s exact test if proper between patients treated with and without the RIPC technique.
The subgroup analysis of the key endpoint using propofol for anesthesia maintenance was examined using a 2-sided Pearson’s χ2 test or Fisher’s exact test if proper between patients treated with and without the RIPC technique.
The sample size of the previous clinical trial of 7-days post operation was based on our retrospective cohort study , we estimated that 75% of participants in the sham group would develop into AKI after surgery. The expected absolute risk reduction for AKI was 25% according to the result of the pilot study. Accordingly, to detect a 25% absolute risk reduction in the primary end point in the RIPC group (from 75% to 50%), with a power of 80% and a significance level of 5%, the result of the sample size was total 116 (total 130 including drop-out data).
A p value < 0.05 indicated significance. SPSS version 20.0 (IBM Corp, Armonk, NY) was employed for statistical analysis. All results were considered explorative.