A Randomized Trial of Intravenous Amino Acids for Kidney Protection.

BACKGROUND: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. METHODS: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. RESULTS: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. CONCLUSIONS: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.).

Intravenous amino acid therapy for kidney protection in cardiac surgery a protocol for a multi-centre randomized blinded placebo controlled clinical trial. The PROTECTION trial.

BACKGROUND: Postoperative acute kidney injury (AKI) is frequent in cardiac surgery patients. Its pathophysiology is complex and involves decreased renal perfusion. Preliminary clinical evidence in critically ill patients shows that amino acids infusion increases renal blood flow and may decrease the incidence and severity of AKI. We designed a study to evaluate the effectiveness of perioperative continuous infusion of amino acids in decreasing AKI. METHODS: This is a phase III, multi-center, randomized, double-blind, placebo-controlled trial. Adults undergoing cardiac surgery with cardiopulmonary bypass (CPB) are included. Patients are randomly assigned to receive either continuous infusion of a balanced mixture of amino acids in a dose of 2 g/kg ideal body weight/day or placebo (balanced crystalloid solution) from the operating room up to start of renal replacement therapy (RRT), or ICU discharge, or 72 h after the first dose. The primary outcome is the incidence of AKI during hospital stay defined by KDIGO (Kidney Disease: Improving Global Outcomes). Secondary outcomes include the need for, and duration of, RRT, mechanical ventilation; ICU and hospital length of stay; all-cause mortality at ICU, hospital discharge, 30, 90, and 180 days after randomization; quality of life at 180 days. Data will be analyzed in 3500 patients on an intention-to-treat basis. DISCUSSION: The trial is ongoing and currently recruiting. It will be one of the first randomized controlled studies to assess the relationship between amino acids use and kidney injury in cardiac surgery. If our hypothesis is confirmed, this practice could reduce morbidity in the studied population. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov with the trial identification NCT03709264 in October 2018.

Performance of EuroSCORE in CABG and off-pump coronary artery bypass grafting: single institution experience and meta-analysis.

AIMS: To assess EuroSCORE performance in predicting in-hospital mortality in on-pump coronary artery bypass grafting (CABG) and off-pump coronary artery bypass grafting (OPCAB). METHODS AND RESULTS: Additive and logistic EuroSCORE were computed for consecutive patients undergoing CABG (n = 3440, 75%) or OPCAB (n = 1140, 25%) at our hospital from 1999 to September 2007. The areas under the receiver operating characteristic (ROC) curves (AUCs) were used to describe performance and accuracy. No difference in performance between CABG and OPCAB and between additive and logistic EuroSCORE (additive EuroSCORE AUCs of 0.808 and 0.779 for CABG and OPCAB, respectively; logistic EuroSCORE AUCs of 0.813 and of 0.773 for CABG and OPCAB, respectively) was found, although a marked tendency to overpredict mortality by both models was evident. A meta-analysis of previously published data was done, and a total of eight studies representing 19 212 and 5461 patients undergoing CABG and OPCAB, respectively, met inclusion criteria. Meta-analysis confirmed similar performance of EuroSCORE in CABG and OPCAB: estimated AUCs were 0.767 and 0.766 for CABG and OPCAB, respectively, with an estimated difference of 0.001 (95% CI -0.061 to 0.063). CONCLUSION: Additive and logistic EuroSCORE algorithms performed similarly, and cumulative evidence suggests comparable performance in CABG and OPCAB procedures; both risk models, however, significantly overestimated mortality.

High thoracic epidural anesthesia in coronary artery bypass surgery: a propensity-matched study.

OBJECTIVES: To assess if 2 different anesthesia strategies, high-thoracic epidural anesthesia (HTEA) plus inhalation anesthesia and total intravenous anesthesia (TIVA) with sufentanil/propofol had different influence on outcomes of coronary artery bypass graft (CABG) surgery patients. DESIGN: Retrospective comparison of outcomes between HTEA and TIVA patients using propensity score pair-wise matching of patients. SETTING: A university teaching hospital. PARTICIPANTS: A study of 1,473 consecutive patients undergoing elective CABG surgery; of these, 476 (32%) received HTEA combined with inhalation anesthesia, whereas 997 (68%) underwent TIVA alone. INTERVENTIONS: The patients undergoing CABG surgery were offered the epidural-inhalation anesthetic approach. MEASUREMENTS AND MAIN RESULTS: Propensity matching yielded 389 pairs of patients. Patients were well matched in preoperative and operative features. Postoperative mortality, myocardial infarction, stroke, acute renal failure rates, and intensive care unit (ICU) stay were not statistically different in HTEA and TIVA groups. On the other hand, patients treated with HTEA had shorter ventilation times (5.8 +/- 3.11 v 6.9 +/- 5.0 hours, HTEA and TIVA, respectively, p < 0.001); in addition, vasoconstrictors were more frequently used in cases of HTEA, whereas vasodilators were mainly used with TIVA both intra- and postoperatively. No neurologic complications related to the use of HTEA were observed. CONCLUSIONS: HTEA and TIVA provided similar early outcomes after CABG surgery, and there were no major differences between these 2 strategies in the average risk CABG patient populations. Although HTEA did not cause neurologic problems and yielded a significant reduction in time to extubation, a consistent benefit over standard techniques could not be shown.

High thoracic epidural anesthesia for off-pump coronary artery bypass surgery.

OBJECTIVE: To assess the feasibility of high thoracic epidural anesthesia combined with sevoflurane for off-pump coronary artery bypass surgery and to evaluate the postoperative pain control, side effects, and perioperative hemodynamics. DESIGN: Retrospective review of prospectively collected data. SETTING: A university teaching hospital. PARTICIPANTS: One hundred six consecutive patients receiving thoracic epidural combined with sevoflurane. INTERVENTION: From November 1999, the patients undergoing off-pump coronary artery bypass grafting were offered the epidural-inhalation anesthetic approach. MEASUREMENTS AND MAIN RESULTS: Insertion of the epidural catheter was successful in all but 2 patients; 1 bloody tap occurred and the dura was never punctured, although 1 patient presented with postoperative paraplegia. An emergency spinal cord nuclear magnetic resonance excluded signs of medullary compression caused by epidural or spinal hematoma. Visual analog scale scores for pain during the first 24-hour period were < 2 in all patients. Mean time to extubation was 4.6 +/- 2.9 hours. The average intensive care unit stay was 1.5 +/- 0.8 days. Incidences of perioperative myocardial infarction, myocardial ischemia, and atrial fibrillation were 2.8%, 7.5%, and 10.6%, respectively. Two patients died: 1 from multiorgan failure and the other from myocardial infarction. Heart rate, mean arterial pressure, cardiac index, and systemic vascular resistance were not affected by thoracic epidural alone. Mean arterial pressure and cardiac index decreased (p < 0.05) when general anesthesia was induced and remained stable thereafter. Neither heart rate nor systemic vascular resistance changed from baseline during operation. CONCLUSIONS: Thoracic epidural as an adjunct to general anesthesia is a feasible technique in off-pump coronary artery bypass surgery. It induces intense postoperative analgesia and does not compromise central hemodynamics.

Oxygen metabolism during and after cardiac surgery: role of CPB.

BACKGROUND: Cardiopulmonary bypass (CPB) has been reported to increase oxygen metabolism and to influence the relation between oxygen consumption (VO(2)) and delivery (DO(2)) in the early hours after cardiac surgery. To investigate the role of CPB, we studied oxygen metabolism in coronary artery bypass procedures performed on-pump (CABG) and off-pump (OPCAB). METHODS: Twenty-five patients were randomized to undergo CABG (n = 14) or OPCAB (n = 11). All patients received the same anesthetic management. Oxygen metabolism variables were assessed before induction of anesthesia and up to 18-hours after surgery. RESULTS: At baseline, before induction of anesthesia, there were no differences between CABG and OPCAB in oxygen consumption (VO(2)), delivery (DO(2)), or extraction (ExO(2)). After surgery VO(2) and ExO(2) increased in both groups, while DO(2) decreased. No significant differences between CABG and OPCAB were detected in postoperative VO(2), DO(2), and ExO(2) levels. The relation between VO(2) and DO(2) was very similar in CABG and OPCAB patients throughout the study, and no significant differences were detected in slopes and intercepts of the regression lines between CABG and OPCAB at all time points. There was, however, a significant effect of time on the relation between VO(2) and DO(2): this relation was stronger in the postoperative period, and the slope of this relation increased over time as well. CONCLUSIONS: A hypermetabolic state and progressive and significant increases in the strength of the relationship between VO(2) and DO(2) and in the slope of this relationship occur after both CABG and OPCAB. Cardiopulmonary bypass is not responsible for these changes in oxygen metabolism.