Dataset Information

Effect of Out-of-Hospital Sodium Nitrite on Survival to Hospital Admission After Cardiac Arrest: A Randomized Clinical Trial.

ABSTRACT:

Importance

Therapeutic delivery of sodium nitrite during resuscitation improved survival in animal models of cardiac arrest, but efficacy has not been evaluated in clinical trials in humans.

Objective

To determine whether parenteral administration of sodium nitrite given by paramedics during resuscitation for out-of-hospital cardiac arrest improved survival to hospital admission.

Design, setting, and participants

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. Patients underwent resuscitation by paramedics and were enrolled between February 8, 2018, and August 19, 2019; follow-up and data abstraction were completed by December 31, 2019.

Interventions

Eligible patients with out-of-hospital cardiac arrest were randomized (1:1:1) 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.

Main outcomes and measures

The primary outcome was survival to hospital admission and was evaluated with 1-sided hypothesis testing. The secondary outcomes included 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 (survival to hospital discharge; neurological outcomes at hospital discharge; cumulative survival to 24 hours, 48 hours, and 72 hours; and number of days in the intensive care unit).

Results

Among 1502 patients with out-of-hospital cardiac arrest who were randomized (mean age, 64 years [SD, 17 years]; 34% were women), 99% completed the trial. Overall, 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 mean difference for the 45-mg dose vs placebo was -2.9% (1-sided 95% CI, -8.0% to ∞; P = .82) and the mean difference for the 60-mg dose vs placebo was -1.3% (1-sided 95% CI, -6.5% to ∞; P = .66). None of the 7 prespecified secondary outcomes were 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; the mean difference for the 45-mg dose vs placebo was -1.7% (2-sided 95% CI, -6.0% to 2.6%; P = .44) and the mean difference for the 60-mg dose vs placebo was -0.4% (2-sided 95% CI, -4.9% to 4.0%; P = .85).

Conclusions and relevance

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.

Trial registration

ClinicalTrials.gov Identifier: NCT03452917.

SUBMITTER: Kim F

PROVIDER: S-EPMC7804921 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe literature is unresolved on whether female receive advanced cardiac life support less than do male and on whether female have a survival advantage over male after cardiopulmonary resuscitation.MethodsWe systematically searched PubMed, Embase and Web of Science databases (from inception to 23-April-2022) for papers reporting outcomes in adult male and female after out-of-hospital cardiac arrest. The main study outcome was the rate of adjusted survival to hospital discharge or 30 days. Secondary outcomes included unadjusted survival to hospital discharge and favourable neurological outcome.ResultsA total of 28 studies were included, involving 1,931,123 patients. Female were older than male, their cardiac arrests were less likely to be witnessed and less likely to present with a shockable rhythm. Unadjusted analysis showed that females had a lower likelihood of survival than males (OR 0.68 [0.62-0.74], I2 = 97%). After adjustment, no significant difference was identified between male and female in survival at hospital discharge/30 days (OR 1.01 [0.93-1.11], I2 = 87%). Data showed that male had a significantly higher likelihood of favorable neurological outcome in unadjusted analysis but this trend disappeared after adjustment. Both the primary outcome (adjusted for several variables) and the secondary outcomes were associated with substantial heterogeneity. The variables examined using meta-regression, subgroup and sensitivity analyses (i.e., study type, location, years, population, quality of adjustment, risk of bias) did not reduce heterogeneity.ConclusionsThe adjusted rate of survival to hospital discharge/30 days was similar for male and female despite an initial seeming survival advantage for male. The validity of this finding is limited by substantial heterogeneity despite in-depth investigation of its causes, which raises concerns regarding latent inequalities in some reports nonetheless. Further study on this topic may require inclusion of factors not reported in the Utstein template and in-depth analysis of decision-making processes.