Impact of Cardiopulmonary Bypass Duration on the Renal Effects of Amino Acids Infusion in Cardiac Surgery Patients

Abstract

Objective: To test whether the duration of cardiopulmonary bypass (CPB) affects the nephroprotective effect of amino acids (AA) infusion in decreasing the occurrence of acute kidney injury (AKI) among cardiac surgery patients.

Design: A post hoc study of the PROTECTION multicenter randomized double-blind placebo-controlled trial aiming to assess the effect of CPB duration on the differential impact of AA infusion on both the absolute and relative risk reduction in AKI incidence by comparing medians of CPB duration and CPB duration as a continuous variable.

Setting: International, multicenter.

Participants: The entire population of the PROTECTION trial, comprising 3511 adult patients undergoing cardiac surgery with CPB.

Interventions: Intravenous AA infusion at a dosage of 2 g/kg/day, up to a maximum of 100 g/day.

Measurements and main results: Compared with patients with CPB duration above the median (prolonged [P]-CPB group), patients with CPB duration below the median (brief [B]-CPB group) had a significantly lower incidence of AKI (23% [n/N =391/1716] vs 36% [n/N = 617/1723]; relative risk [RR], 0.64; 95% confidence interval [CI], 0.57-0.71; p <0.001). However, in the P-CPB group, AA infusion achieved an 8% absolute risk reduction (32% vs 40%) and a 0.79 RR reduction (95% CI, 0.70-0.90; p < 0.001; number needed to treat, 14). Moreover, AA also decreased the occurrence of AKI stage 3 (2.2% [n = 19] vs 5.0% [n = 43]; RR, 0.45; 95% CI, 0.26-0.76; p < 0.001) with a >95% probability of this effect being significantly greater in the P-CPB group compared to the B-CPB group.

Conclusions: Cardiac surgery patients with prolonged CPB exposure had a significantly higher incidence of AKI. Notably, the P-CPB group received a greater benefit from AA therapy with an absolute risk and relative risk reduction of both any and severe AKI compared with the B-CPB group. Patients with prolonged CPB may be the specific targets of future studies.

Keywords: acute kidney injury; amino acids; anesthesia; cardiac surgery; cardiopulmonary bypass; intensive care.