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.

Oxidative stress and liver monooxygenase function after heart valve surgery.

BACKGROUND AND OBJECTIVES: this prospective study was carried out to evaluate oxidative stress and liver monooxygenase function after cardiac surgery in patients with acquired valvular heart disease. METHODS: 97 patients were studied. Oxidative stress was quantified with malondialdehyde, coupled trienes, hepatocuprein, and catalase activity. Liver monooxygenase function was evaluated with antipyrine pharmacokinetics. For statistical analyses, the Dunnett test and Pearson's correlation coefficient were used. RESULTS: on the 1st-2nd postoperative days, high lipid peroxidation activation (malondialdehyde: 9.6 ± 2.7 vs. 6.9 ± 2.0 nmol mL(-1), p <0.05) and a significant decrease in liver monooxygenase function (antipyrine clearance: 18.3 ± 11.1 vs. 39.0 ± 18.9 mL kg(-1)h(-1), p <0.05) were revealed. On the 3rd-4th and 11th-12th postoperative days, the intensity of oxidative stress decreased and monooxygenase function returned to baseline (antipyrine clearance: 45.6 ± 17.9 vs. 39.0 ± 18.9 mL kg(-1)h(-1)). The analysis showed a negative relationship between oxidative stress and liver monooxygenase function. CONCLUSION: patients undergoing surgery for acquired valvular heart disease have considerable oxidative stress and a decrease in liver monooxygenase function on the 1st-2nd postoperative days. Activation of lipid peroxidation is one of the main reasons for suppression of microsomal monooxygenases activity. A slowdown of liver microsomal oxidation might change the pharmacokinetic response of patients under drug therapy.