Sodium nitrite not effective for resuscitation in out-of-hospital cardiac arrest
Out-of-hospital cardiac arrest is a common cause of premature morbidity and mortality and hence a major public health challenge. A recent study suggests among patients with out-of-hospital cardiac arrest, administration of sodium nitrite, compared with placebo did not significantly improve the survival rate of the patient. The study findings were published in the journal JAMA on January 12, 2021.
Previous studies reported that despite advances in resuscitation, more than 80% of those in whom circulation was restored after out-of-hospital cardiac arrest died before hospital discharge in studies with data collected between 2005 and 2015. Nitrite therapy limits cellular injury and apoptosis after ischemia and reperfusion and nitrite therapy is cytoprotective in numerous animal models of focal ischemia. Preclinical studies in nitrite therapy during the early reperfusion period following cardiac arrest are associated with improved survival rate. However, the efficacy has not been evaluated in clinical trials in humans. Therefore, researchers of the University of Washington, Seattle, conducted a study determine whether parenteral administration of sodium nitrite given by paramedics during resuscitation for out-of-hospital cardiac arrest improved survival to hospital admission.
It was a double-blind, placebo-controlled, phase 2 randomized clinical trial including 1502 adults in King County, Washington, with out-of-hospital cardiac arrest from ventricular fibrillation or nonventricular fibrillation. Researchers randomized the patients to receive 45 mg of sodium nitrite (n = 500), 60 mg of sodium nitrite (n = 498), or placebo (n = 499), which was given via bolus injection by the paramedics as soon as possible during active resuscitation. The major outcome assessed was the survival to hospital admission and was evaluated with 1-sided hypothesis testing. They also assessed out-of-hospital variables (rate of return of spontaneous circulation, rate of rearrest, and use of norepinephrine to support blood pressure) and in-hospital variables.
Key findings of the study were:
• A total of 205 patients (41%) in the 45 mg of sodium nitrite group and 212 patients (43%) in the 60 mg of sodium nitrite group compared with 218 patients (44%) in the placebo group survived to hospital admission.
• The researchers observed that the mean difference for the 45-mg dose vs placebo was −2.9% and the mean difference for the 60-mg dose vs placebo was −1.3%.
• They noted that none of the 7 prespecified secondary outcomes was significantly different, including survival to hospital discharge for 66 patients (13.2%) in the 45 mg of sodium nitrite group and 72 patients (14.5%) in the 60 mg of sodium nitrite group compared with 74 patients (14.9%) in the placebo group.
• They also noted that the mean difference for the 45-mg dose vs placebo was −1.7% and the mean difference for the 60-mg dose vs placebo was −0.4%.
The authors concluded, "Among patients with out-of-hospital cardiac arrest, administration of sodium nitrite, compared with placebo, did not significantly improve survival to hospital admission. These findings do not support the use of sodium nitrite during resuscitation from out-of-hospital cardiac arrest".
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