The RCT was performed in the Departments of Anesthesiology and Cardiovascular Surgery of Xijing Hospital, Xian, China, and included 244 adults (mean age 48) undergoing elective, multiple valve replacement surgery (requiring 90 minutes or more cardiopulmonary bypass), mostly due to rheumatic fever, which is responsible for more than half a million deaths in Asia each year. Patients received either NO (treatment - 80 parts-per-million) or nitrogen N2 (control).
The hypothesis was that administration of 80ppm NO during and for 24h after surgery would convert plasma Oxy-Hb to Met-Hb and prevent intrarenal oxidative reactions and NO scavenging by plasma Oxy-Hb, and thus preserve kidney function.
Primary outcome - Incidence of AKI within 7 days
This was defined as an increase of serum creatinine by 50% within 7 days after surgery, or an increase of serum creatinine by 0.3 mg/dl within 2 days after surgery from preoperative baseline levels of serum creatinine.
Secondary outcomes - Development of stage 3 CKD (eGFR<60 mL/min/1.73m2)26-27, loss of 25% of eGFR compared to baseline, and major adverse kidney events (defined as a composite outcome of loss of 25% of eGFR from baseline, end stage renal disease requiring a continuous renal replacement therapy and
mortality)25 at 30 days, 90 days, and 1 year following ICU admission.
Stage 3 chronic kidney disease at 90 days
Stage 3 chronic kidney disease at 1 year
Major adverse kidney events were fewer in the NO group at 30d, 90d and 1 year.
There was no difference between the groups in other intra-hospital outcomes or long-term outcome variables, including hospital readmission rate and mortality up to 1 year. Although the study was not powered to test whether NO exposure could reduce mortality, at 1 year, the rate of mortality in the NO treatment group was 3% (3/117) compared to 6% (8/127) in the control group.
The researchers conclude: “Nitric oxide gas is the first pharmacological intervention to show a reduction in the incidence of acute kidney injury and an improvement of long-term kidney function in cardiac-surgical patients after prolonged cardiopulmonary bypass”. They recommend that the findings should be assessed in non-Chinese patients without rheumatic fever as the study is also limited by the young mean age of patients and the absence of pre-operative severe chronic kidney disease and other cardio-vascular comorbidities in the patient cohort.
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