Postoperative acute kidney injury (AKI) in cardiac surgery represents a severe complication associated with increased morbidity and mortality. Its development is mediated by reduced renal blood flow induced by a variety of factors, including endogenous and exogenous toxins, metabolic disturbances, ischemia-reperfusion injury, and the use of cardiopulmonary bypass (CPB) itself. Several authors have identified oxygen delivery (DO2) during CPB as a critical factor in AKI, estimating a critical threshold for DO2 between 225 and 300 mL/min/m².

This study is a prospective, randomized, blinded, single-center trial with a sample of 300 cardiac surgery patients. Patients with chronic renal failure, circulatory arrest, CPB temperature below 34ºC, or postoperative need for ECMO or intra-aortic balloon pump were excluded. The primary objective was to assess the incidence of postoperative AKI based on KDIGO criteria. Secondary objectives included red blood cell transfusion rates, mechanical ventilation duration, ICU and hospital length of stay, peak serum creatinine 48 hours post-surgery, and perioperative mortality.

The sample consisted of 127 patients in the DO2i-guided perfusion strategy group and 138 in the conventional strategy (CS) group. In the DO2i group, DO2 was adjusted by modifying pump flow, initially set at 2.6 L/min/m², and by red blood cell transfusion when hemoglobin levels dropped below 8.5 g/dL, a threshold deemed sufficient to maintain DO2 above the critical level. The CS group relied on a fixed pump flow of 2.6 L/min/m² based solely on the patient’s body surface area (BSA). Red blood cell transfusion was performed when hemoglobin dropped below 7 g/dL. Both groups maintained normothermia (temperature >35ºC) and a mean arterial pressure (MAP) >60 mmHg.

Pre- and intraoperative variables were comparable between groups. However, the DO2i group exhibited a higher pump flow rate, with an average index of 2.82 L/min/m² compared to 2.63 L/min/m² in the CS group (p < .001). Using real-time gas monitoring (Terumo® CDI 500®) and data logging with the Livanova® Connect® system, it was observed that the area under the curve (AUC) for DO2i <300 mL/min/m², as well as for venous oxygen saturation (SvO2) <70 mmHg and MAP <60 mmHg, were consistently lower in the DO2i group (p < .001). This translated to significantly lower times with DO2i <300 mL/min/m² (DO2i 2.7 min vs. CS 20.3 min, p < .001), SvO2 <70 mmHg (DO2i 0 min vs. CS 0.7 min; p < .001), or MAP <60 mmHg (DO2i 19 min vs. CS 24.8 min; p < .005) in the DO2i group. Consequently, the AKI incidence in the DO2i group was 14.6% versus 30.4% in the CS group (RR = 0.48; p = .002). Significant differences were only observed for KDIGO stage 1 AKI (DO2i 12.4% vs. CS 25.4%, RR = 0.42; p = .006), with no differences in stages 2 and 3. No significant differences were found in red blood cell units transfused, ventilation time, ICU and hospital stays, peak serum creatinine at 48 hours post-surgery, or postoperative mortality.

A univariate logistic regression analysis showed that perioperative variables associated with AKI included time with DO2i <300 mL/min/m² (p = .023), age (p = .013), baseline glomerular filtration rate (p = .001), surgical technique (p = .006), and perfusion time (p = .004). In multivariate analysis, only perfusion time remained significantly associated (p = .024) with increased AKI incidence.

The main finding of this study suggests that in subgroup analysis, DO2i proved superior for protecting against postoperative AKI in patients aged 60 to 74 years, with a BSA <1.4 m², baseline glomerular filtration rate of 60-89 mL/min/1.73 m², nadir hematocrit <23%, and CPB duration <120 min.

COMMENTARY:

This single-center study, with a limited sample, analyzed small subgroups, thus limiting the validity of the conclusions. However, as a perfusionist, I believe it is crucial to have as much information as possible during CPB through continuous gas monitoring systems that measure gasometric values and oxygen consumption (VO2) as well as hemoglobin levels. The addition of the Livanova® Connect® system, which logs data in real-time and calculates DO2i by integrating perfusion variables such as pressures, flows, gas values, and medication administration, provides essential data to optimize patient conditions during cardiopulmonary bypass and allows real-world data for ongoing research aimed at improving perfusion and reducing its adverse effects.

According to the study’s findings, it is evident that maintaining elevated hemoglobin levels in all patients or increasing perfusion flow above 3 L/min/m² to achieve acceptable DO2i values is not the solution, as both have demonstrated detrimental effects: higher transfusion rates increase morbidity and mortality in cardiac surgery, and higher pump flow leads to hemodilution, hemoglobinuria, which predisposes to AKI, and increased inflammatory response and coagulation issues. DO2i is particularly effective in patients with low BSA who are more sensitive to hemodilution, struggle to maintain adequate DO2, and in patients with nadir hematocrit <23%.

However, due to the detrimental nature of CPB, its duration remains the main factor associated with AKI in multivariate analysis. The role of DO2i is still unclear, and further research is needed to establish the optimal balance between pump flow and red blood cell transfusion. Future studies with real-time data systems like Livanova® Connect® will provide valuable insights for identifying patient characteristics that respond best to each strategy.

REFERENCE:

Mukaida H, Matsushita S, Yamamoto T, Minami Y, Sato G, Asai T, Amano A. Oxygen delivery-guided perfusion for the prevention of acute kidney injury: A randomized controlled trial. J Thorac Cardiovasc Surg. 2023 Feb;165(2):750-760.e5. doi: 10.1016/j.jtcvs.2021.03.032.