Usefulness of Intravenous Sodium Nitrite During Resuscitation for the Treatment of Out-of-Hospital Cardiac Arrest

Abstract

It is hypothesized that intravenous (IV) sodium nitrite given during resuscitation of out-of-hospital cardiac arrest (OHCA) will improve survival. We performed a phase 1 open-label study of IV sodium nitrite given during resuscitation of 120 patents with OHCA from ventricular fibrillation or nonventricular fibrillation initial rhythms by Seattle Fire Department paramedics. A total of 59 patients received 25 mg (low) and 61 patients received 60 mg (high) of sodium nitrite during resuscitation from OHCA. Treatment effects were compared between high- and low-dose nitrite groups, and all patients in a concurrent local Emergency Medical Services registry of OHCA. Whole blood nitrite levels were measured in 97 patients. The rate of return of spontaneous circulation (48% vs 49%), rearrest in the field (15% vs 25%), use of norepinephrine (12% vs 12%), first systolic blood pressure (124 ± 32 vs 125 ± 38 mm Hg), survival to discharge (23.7% vs 16.4%), and neurologically favorable survival (18.6% vs 11.5%) were not significantly different in the low and high nitrite groups. There were no significant differences in these outcomes among patients who received IV nitrite compared with concurrent registry controls. We estimate that 60 mg achieves whole blood nitrite levels of 22 to 38 μM 10 minutes after administration, whereas 25 mg achieves a level of 9 to 16 μM 10 minutes after delivery. In conclusion, administration of IV nitrite is feasible and appears to be safe in patients with OHCA, permitting subsequent evaluation of the effectiveness of IV nitrite for the treatment of OHCA.

Trial registration: ClinicalTrials.gov NCT02987088.

Copyright © 2018 Elsevier Inc. All rights reserved.

Figures

Figure 1.

Study flow diagram describing the number of patients eligible, enrolled, and outcomes. Abbreviations: IV-intravenous, IO-intraosseous, ALS- Advanced life support, ROSC-return of spontaneous circulation, VF-ventricular fibrillation.

Figure 2.

Complete whole blood nitrite levels after OHCA. The three black dotted overlay lines represent the predicted nitrite levels based upon PK parameters obtained in 3 lung transplant subjects with repeated sampling assuming a dose of 25 mg (A) or 60 mg (B) of nitrite given IV over 0.5 min. Overlaying these predicted ranges are the actual measured whole blood nitrite levels in units of μM based on the time the blood was obtained relative to the time of nitrite dosing (0 min) during CPR. The patients’ vital status at the time of blood draw is represented by the color/type of symbol used as shown in the key.