Title : Effect of ascorbic acid on postoperative acute kidney injury in moderate to high-risk patients undergoing valvular heart surgery: A single center randomized controlled trial
Abstract:
Acute kidney injury (AKI) is a common and devastating complication of valvular heart surgery with cardiopulmonary bypass (CPB). The anti-inflammatory, antioxidant, and vasopressor-sparing effects of ascorbic acid (AA) have been validated in patients with sepsis and septic shock. However, these effects are less studied in cardiac surgical patients, particularly those at moderate to high risk of postoperative AKI. Considering the risk factors for AKI following cardiac surgery with CPB—such as hypotension/hemodynamic instability, oxidative stress from ischemia-reperfusion injury, and inflammation—AA’s protective effects may help reduce AKI incidence, especially in vulnerable patients. This study aimed to investigate the effect of perioperative AA administration on AKI in patients at moderate to high risk of developing AKI after valvular heart surgery with CPB.
Patients scheduled for on-pump valvular heart surgery were randomly assigned to the AA or control group. The AA group received 1500 mg of AA intravenously the night before surgery, and 1500 mg before aortic clamp removal, then at 3, 9, 15, and 21 hours post-ICU arrival. The control group received an equivalent volume of normal saline at the same time points. The primary endpoint was the incidence of AKI as defined by the Kidney Disease: Improving Global Outcomes criteria. Secondary endpoints included major morbidity outcomes. Malondialdehyde, thrombomodulin, and vitamin C levels were measured before surgery and immediately after CPB.
The trial initially planned to enroll a total of 258 patients; however, an interim analysis was conducted when approximately 50% of the target enrollment was reached. The trial was terminated early due to futility based on interim analysis, with outcomes assessed in 131 patients (66 AA-treated, 65 control). Both groups were comparable in baseline demographics and intraoperative characteristics. The incidence of AKI was similar between the groups (23% [AA-treated] vs. 14% [control], P = 0.277). Other outcome variables, including perioperative vasoplegia, stroke, and mortality, were also similar. Malondialdehyde and thrombomodulin levels were higher after CPB compared to before. No significant intergroup differences were observed over time in malondialdehyde, thrombomodulin, or vitamin C levels. There were no significant differences in hemodynamic parameters or vasopressor dosage from the day of surgery to two days postoperatively.
In patients at moderate to high risk of developing postoperative AKI, perioperative AA administration over 24 hours did not effectively attenuate serum markers of oxidative stress, endothelial injury or systemic inflammation. Subsequently, this AA regimen could not reduce the risk of AKI development following valvular heart using CPB.
