ORLANDO, Fla. — Nitric oxide may reduce the incidence of acute kidney injury (AKI) after complex cardiac surgery, according to a new prospective study presented at the American Heart Association Scientific Sessions.

Lorenzo Berra, MD, who is an assistant professor of anesthesia at Harvard Medical School in Boston, Massachusetts, and colleagues conducted a trial with 217 patients with normal pre-operative kidney function who were having elective multiple valve replacement requiring cardiopulmonary bypass.

The patients were randomized into 2 groups. The first group received standard of care and the second group was treated with 80 parts per million (ppm) of nitric oxide during cardiopulmonary bypass and for 24 hours after surgery.


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The most common complication associated with prolonged cardiopulmonary bypass is AKI, which markedly increases the death rate. This trial addressed the question of whether nitric oxide administration during and after prolonged cardiopulmonary bypass can reduce AKI.  The researchers found that administration of nitric oxide significantly decreased the incidence of AKI from 63% in the control group to 50% in the nitric oxide-treated patients.

The researchers theorized that nitric oxide may be renal protective by 3 possible mechanisms. One mechanism proposed is that selective vasodilation of the pulmonary circulation leads to increased cardiac output and renal perfusion. A second mechanism may be that nitric oxide reduces ischemia-reperfusion renal injury. A third potential mechanism may be oxidation of plasma Hb to metHb, which cannot scavenge nitric oxide.

This single center, prospective, randomized, double-blind controlled trial investigated whether nitric oxide can reduce AKI (primary outcome), and other major complications immediately post-surgery, at 30 days, and 90 days (secondary outcomes). For this investigation, the researchers defined AKI as either an increase of serum creatinine by 50% within 7 days after surgery or an increase of serum creatinine by 0.3 mg/dL within 48 hrs. The mean age of the cohort was 48 years and the mean BMI was 22 kg/m2. The control group was 63% female and the treatment group was 56% female.

Overall, the study showed that administration of 80 ppm of nitric oxide for 24 hours was safe and blood metHb was always below 10%. The researchers reported that oxidation of plasma Hb may reduce the incidence of AKI by reducing plasma consumption of nitric oxide and by other therapeutic effects of nitric oxide therapy. In this study, there were 6 deaths in the control arm but only 2 deaths in the nitric oxide arm.

The researchers stated further studies are warranted and these findings need to be validated in a larger and more diverse patient population. In part, they explained, because this study was conducted in China and these patients had different profiles than their American counterparts. They found that compared with Western patients undergoing prolonged cardiopulmonary bypass, the Chinese patients in this trial were younger, thinner, and had fewer co-existing diseases.

Raymond Gibbons, MD, who is a past president of the American Heart Association and a professor of medicine at the Mayo Clinic in Rochester, Minnesota, said these study findings are very encouraging. However, he said more studies with different patient populations are warranted before clinicians can start using this agent off-label to prevent AKI.

“This was an unusual patient population and very long times on bypass. It has to be tested in a more diverse group,” Dr Gibbons told Cardiology Advisor. “The benefits were significant but they were not huge. Shorter pump time is something that has to be looked at. What is the best duration?”

Dr Gibbons said keeping the patients in the ICU for 24 hours on nitric acid may not be necessary and future studies need to determine the optimal use of this agent in this setting.

References

Berra L. LBCT.04—Novel Therapies for Common Problems. Prevention of Acute Kidney Injury by Nitric Oxide During and After Prolonged Cardioplumonary Bypass. A Double Blind Randomized Controlled Trial. Presented at the American Heart Association Scientific Sessions; November 7-11, 2015; Orlando, FL.