Sodium Nitrite Disappoints in Cardiac Arrest

April 14, 2020

Among patients who had an out-of-hospital cardiac arrest, intravenous sodium nitrite given by paramedics during resuscitation did not significantly improve their chances of being admitted to or discharged from the hospital alive.

The study was presented at the recent "virtual" American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC).

Lead investigator Francis Kim, MD, professor of medicine at the University of Washington, Seattle, explained that sodium nitrate is an antioxidant; animal studies have suggested that under conditions of hypoxia, it is converted into the vasodilator nitric oxide, which can increase blood flow to the brain and heart tissues.

In animal models of cardiac arrest, the use of sodium nitrite during resuscitation increased survival by almost 50%.

For the current study, 1502 patients who had an out-of-hospital cardiac arrest were randomly assigned to receive either a low dose (45 mg) or a high dose (60 mg) of sodium nitrite or a placebo. The average age of the patients who were included in the study was 64 years, and 66% were male; 22% had ventricular fibrillation, 43% had asystole, and 29% had pulseless electrical activity.

Results showed no statistically significant differences between the groups who received placebo, low-dose sodium nitrite, or high-dose sodium nitrite on survival to hospital admission (the primary endpoint) or on hospital discharge (the secondary endpoint). There was also no difference in either endpoint in the subgroup with ventricular fibrillation.

"Our results are disappointing, especially after the promising findings in animal studies, but we feel this trial shuts the door on using this drug in this indication," Kim said.

Discussing the study at an ACC press conference, Dhanunjaya Lakkireddy, MD, University of Kansas Hospital and Medical Center and ACC Electrophysiology Council chair, said this was "an excellent trial in the unending quest to try to improve survival in out-of-hospital cardiac arrest.

"As we all aware, if we don't get blood circulation to the brain for more than 5 seconds, we pass out, and if don't get blood circulation to the brain for more than 5 minutes, brain death occurs. When people suffer out-of-hospital cardiac arrest, the rate of survival is therefore dramatically lower when the ability to resuscitate goes beyond 5 minutes," Lakkireddy noted.

He questioned why the current trial showed no effect when there had been significant early promise in animal studies. He suggested factors that could have been relevant included the time to intervention ― which was an average of 22 minutes from call to randomization ― perfusion of the brain, whether the drug cleared the blood-brain barrier, whether nitric oxide levels in the brain were sufficient, and the patient population that was included in the study.

"A large percentage of patients had asystole or pulseless electrical activity ― these are known to have worse outcomes ― and 60% of patients in the study did not have a witnessed arrest and could have been down for much longer and therefore could have had a significantly higher level of irreversible brain damage," Lakkireddy pointed out.

"If we can understand some of the issues, we may be able to do another trial in a different subset of patients in whom the duration of arrest is significantly lower," he commented.

The study was funded by the National Heart, Lung, and Blood Institute. Kim has disclosed no relevant financial relationships.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC): Abstract 20-LB-20387-ACC. Presented March 29, 2020.

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