The study was approved by the IRB of Federico II University of Naples, Naples, Italy (protocol number 113/19), and was conducted in compliance with the Declaration of Helsinki (1964 and following amendments), current Good Clinical Practices, and the applicable European and local regulatory requirements.
Patients in our university hospital usually are invited to freely give written informed consent to authorize the use of their clinical data for research purposes. All subjects included in this study provided consent for the use of their data and the local IRB waived the requirement of further written informed consent.
Subjects
This was a retrospective, case-control study conducted at Federico II University Hospital of male and female patients undergoing general anesthesia for kidney transplantation.
Inclusion criteria were age ≥ 18, years, use of sugammadex + rocuronium or neostigmine + cisatracurium during the transplantation, collection of blood, renal and urinary parameters for the first week after the transplantation, no transplant rejection and/or removal of transplanted kidney during the first week. Exclusion criteria were age< 18 years, transplant rejection or removal of transplanted kidney during the first week and concomitant use of nephrotoxic drugs.
We analyzed 113 medical records of patients undergoing kidney transplantation from January 2015 to December 2018. Forty-seven medical records were excluded because they did not report the administration of rocuronium + sugammadex (roc + sug) or cisatracurium + neostigmine (cis + neo) during the transplantation. All patients received the graft from a cadaveric donor. We finally collected data from 66 medical reports.
Interventions
Anesthesia was induced with 1.5 to 2.5 mg/kg propofol and 1 to 2 μg/kg fentanyl. After acceleromyograph calibration, a single dose of 0.6 mg/kg rocuronium or 0.2 mg/kg cisatracurium were administered and tracheal intubation was performed. Additional doses of 0.15 mg/kg rocuronium or 0.03 mg/kg cisatracurium were administered during surgery at TOF2 if required. Anesthesia was maintained by sevoflurane and remifentanil and titrated according to hemodynamic and autonomic responses. At the end of surgery, sevoflurane was decreased to an end-tidal concentration of 0.8% to 1%, and 2 mg/kg sugammadex or 0.05 mg/kg neostigmine were administered when the acceleromyograph registered a TOF2 response.
Data collection and outcome
For each medical records the following data were recorded: age, gender, reason of chronic renal failure, body mass index (BMI), comorbidities, type and dose of neuromuscular blockers and proper reversals, donor age, ischemia time, need of pre and post-operative dialysis, post-operative bleeding. Blood creatinine, blood urea, blood sodium, blood potassium, blood calcium levels were collected at the day before the surgery, the day of surgery, after 6 hours (hrs), 12 hrs, 24 hrs, 48 hrs and 72 hrs. Diuresis, urinary sodium and urinary potassium levels were collected at the day of surgery, after 6 hrs, 12 hrs, 24 hrs, 48 hrs and 72 hrs. Marginal, single or double kidney transplantations, karpinsky score and histologic evaluation of transplanted kidney were collected.
The primary outcome of this study was to evaluate the impact of using rocuronium + sugammadex vs cisatracurium + neostigmine during kidney transplantation on the recovery of kidney function evaluated in terms of serum creatinine and serum urea variations. The secondary outcome was to evaluate if the use rocuronium + sugammadex or cisatracurium + neostigmine were risk factors for kidney failure after kidney transplantation. Acute kidney failure after kidney transplantation was evaluated according KDIGO criteria as increase of creatinine levels of 0.3 mg/dl after 48 hours.
Statistical Analysis
Data are presented as means ± SDs or median and range interquartile. Data were analyzed with 1-way analysis of variance, and distribution of residuals was investigated with the Shapiro-Wilk test.
Comparison between groups were performed with ANOVA for repeated measurement. Any comparison was weighted according the sample size. The Cohen’s d effect size was further calculated on the comparison that reached a statistical significance. The effect size was classified as small (< 0.2), medium (0.2–0.8) and large (>0.8). A univariate logistic regression was performed to identify clinically meaningful variables potentially associated with the risk of post-transplantation renal failure. Thereafter, multiple logistic regressions were carried out using backward stepwise variable elimination, including the variables with a p<0.05 at the univariate analysis. Statistical significance was set at p = 0.05. Statistical analysis was performed using SPSS (version 20.0, IBM®, USA).