Sodium nitrite confers no survival benefit in out-of-hospital cardiac arrest
IV sodium nitrite administered by paramedics for out-of-hospital cardiac arrest had no effect on survival to hospital admission or discharge compared with placebo, according to data presented at the virtual American College of Cardiology Scientific Session.
Moreover, sodium nitrite showed no significant adverse effects on patient hemodynamics compared with placebo.
For this double-blind randomized trial, 1,492 unconscious adult patients with out-of-hospital cardiac arrest were administered IV sodium nitrite (45 mg or 60 mg) or placebo by paramedics approximately 22 minutes from initial call.
Researchers observed no significant difference in survival to hospital admission between the three groups (P > .5). Survival was greater in patients who underwent ventricular fibrillation (P > .05).
Additionally, for survival to hospital discharge, researchers observed no difference between sodium nitrite 60 mg compared with placebo (P = .53) or sodium nitrite 45 mg compared with placebo (P = .21).
“Animal studies have demonstrated that the administration of sodium nitrite during resuscitation improves survival by nearly 50%, and this provided a very compelling rationale to perform this randomized study,” Francis Kim, MD, professor of medicine at the University of Washington, Seattle, said during his presentation. “Unfortunately, in this randomized study of sodium nitrite for out-of-hospital cardiac arrest, we found that sodium nitrite did not significantly improve survival to hospital admission or to discharge. These data suggest that the use of sodium nitride for out-of-hospital cardiac arrest should be abandoned and not pursued further.”
Hemodynamic effects of sodium nitrite
Compared with patients assigned placebo, those treated with 60 mg sodium nitrite had a 5 mm Hg decrease in systolic BP and those treated with 45 mg sodium nitrite had an 8 mm Hg decrease.
Researchers also found no difference between the three groups in patients who were treated with vasopressors for hypotension within the first 24 hours of hospitalization.
“Sodium nitride has a half-life of around 50 minutes, so we would expect to see a small blood pressure effect following the administration of sodium nitrite,” Kim said during the presentation. “Nevertheless, this was not hemodynamically significant.”
This trial was conducted with the assistance of paramedics in Seattle and King County, Washington, and included adults with out-of-hospital cardiac arrest and IV/intraosseous access. Patients were excluded if they were younger than 18 years, experienced traumatic cardiac arrest, had a known do-not-resuscitate order or were a prisoner, pregnant or drowning.
Effect of time to infusion
“The animal work is very compelling, and it makes me wonder if ... time to infusion is the major issue,” Mitchell N. Faddis, MD, PhD, professor of medicine in the cardiovascular division at Washington University School of Medicine in St. Louis, said during the presentation. “That the damage is done. I’m wondering whether or not there would have been a difference if the infusion had gone in earlier.”
Kim said that “The 22 minutes is pretty much the best-case scenario. When we compare our study with other studies, such as the PARAMEDIC-2 trial, time from call to time of epinephrine delivery was about 20 minutes as well. We may be hitting the real-world limitation in terms of how fast we can deliver any kind of drug to help with this being a reperfusion injury.”
The blood-brain barrier
In a press conference, Dhanunjaya R. Lakkireddy, MBBS, FACC, an electrophysiologist and the medical director for the Kansas City Heart Rhythm Institute at HCA Midwest Health, discussed urgency of time and barriers to survival in patients with cardiac arrest.
“When the brain doesn’t get blood circulation for more than 5 seconds, we pass out. If we don’t get that circulation to the brain for more than 5 minutes, we suffer brain death,” Lakkireddy said during the press conference. “That’s one of the primary reasons why when people suffered a cardiac arrest, the rate of survival to the hospital or preserved neurological function for out-of-hospital discharge is dramatically lower.
“If we can understand whether this drug really clears the blood-brain barrier, if early intervention is important, then maybe we need to do a different trial with a different subset of people where the duration of arrest has been significantly lower,” Lakkireddy said. “Nonetheless, our quest to improve the survival of these patients is very important.” – by Scott Buzby
Reference:
Kim F, et al. Late-Breaking Clinical Trials III. Presented at: American College of Cardiology Scientific Session; March 28-30, 2020 (virtual meeting).
Disclosures: Kim, Faddis and Lakkireddy report no relevant financial disclosures. The study was funded by the NHLBI.