Nitric Oxide Reduces Kidney Injury in Surgery with Extended Cardiopulmonary Bypass

November 11, 2015

ORLANDO, FL — An intervention aimed at preventing the vascular depletion of nitric oxide might be a possible target for operators looking to prevent acute kidney injury associated with extended cardiopulmonary bypass during surgery, suggest the results of a new study[1].

In the study, presented this week at the American Heart Association (AHA) 2015 Scientific Sessions, Dr Lorenzo Berra (Massachusetts General Hospital, Boston) reported that the administration of nitric oxide during extended cardiopulmonary bypass for patients undergoing surgical replacement of multiple heart valves significantly reduced acute kidney injury.

"Acute kidney injury is the most common complication after cardiac surgery with prolonged cardiopulmonary bypass," said Berra.

Dr Lorenzo Berra

Speaking with the media, Berra explained that prolonged cardiopulmonary bypass is associated with hemolysis and high levels of free hemoglobin, and this bypass-induced hemolysis causes the depletion of nitric oxide, which is associated with acute kidney injury.

They believe that prolonged cardiopulmonary bypass produces high levels of plasma ferrous oxyhemoglobin, which depletes vascular nitric oxide. The administration of exogenous nitric oxide, on the other hand, causes the oxidation of ferrous oxyhemoglobin and would decrease the risk of kidney injury by reducing the plasma depletion of nitric oxide, said Berra.

In the trial, which was conducted at single center in China, 217 patients undergoing surgery for the replacement of multiple valves were randomized to nitric oxide, which was delivered via the oxygenator during cardiopulmonary bypass and via the ventilator for 24 hours after surgery, or to placebo. In the control and nitric-oxide arms, the duration of cardiopulmonary bypass during surgery was 132 and 137 minutes, respectively.

Overall, acute kidney injury—defined as a 50% increase in serum creatinine within 7 days of surgery or a 0.3-mg/dL increase in serum creatinine within 2 days of surgery—was reduced 22% among individuals who received nitric oxide. In total, acute kidney injury was observed in 63% of the 112 control patients and 50% of the 105 patients who received nitric oxide, a difference that was statistically significant.

Commenting on the results of the study, Dr Stefan Janssens (University of Leuven, Belgium) said, "It is quite clear that acute kidney injury in cardiac surgery is a problem that is very prevalent and has important prognostic implications." Acute injury occurs in nearly one-third of patients, with dialysis required in 1% of patients, and is associated with substantial morbidity and mortality independent of all other risk factors.

To date, no single strategy has been able to prevent acute renal injury, added Janssens.

"Part of the problem, and the reason the conundrum persists, is that the pathogenesis of acute renal injury is quite complex," he said. "In the presence of prolonged cardiopulmonary bypass, there are vasomotor and hemodynamic changes that maybe more important the longer the cardiopulmonary bypass is ongoing. There are changes in reperfusion as a consequence of [bypass], and there are important inflammatory responses and direct nephrotoxic elements that are all contributing to kidney injury and acute renal failure."

Regarding the present study, the results suggest the benefit in preventing acute kidney injury with nitric oxide was predominantly mediated by the lower number of patients who developed stage 1 kidney injury. He noted the trial included only Chinese patients, and these patients were relatively young (mean age 48 years). Future studies will be need to include more patients and different patient populations, as well as need to investigate the potential benefits in surgeries where the cardiopulmonary bypass duration is shorter, such as less than 2 hours.

Berra and Janssens report no relevant financial relationships. Disclosures for the coauthors are listed in the abstract.

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