Drug treatment in out-of-hospital cardiac arrest: Does vascular access route matter?

Lidocaine and amiodarone yield similar gains in survival when used to treat shock-refractory out-of-hospital cardiac arrest (OHCA) relative to placebo, along with a more favourable neurological outcome at hospital discharge when administered intravenously, as shown in a recent study. Conversely, these beneficial effects may not be observed when the drugs are given via the intraosseous route.

“The findings from this study are observational and not clinically definitive, but they are nonetheless provocative,” according to the investigators. “They suggest that amiodarone and lidocaine might each be life-saving drugs in patients with shock-refractory OHCA, although only when they are given intravenously.”

The current report is a prespecified analysis the ALPS trial (Resuscitation Outcomes Consortium Amiodarone, Lidocaine or Placebo Study), where 3,019 patients with OHCA attributable to shock-refractory ventricular fibrillation/pulseless ventricular tachycardia were randomized to receive amiodarone, lidocaine or placebo delivered either intravenously (n=2,358; 78 percent) or by an intraosseous route (n=661; 22 percent).

Patients in the intraosseous and intravenous groups differed in terms of sex, time-to-emergency medical services arrival and several cardiopulmonary resuscitation characteristics, but were similar in others, including time-to-intravenous/intraosseous drug receipt. The rate of survival to hospital discharge, the primary study outcome, was 23 percent in the entire population. [Circulation 2020;141:188-198]

Multivariable linear regression showed that survival to discharge, when compared to patients who received placebo, was significantly higher in recipients of intravenous amiodarone (adjusted risk ratio [RR], 1.26, 95 percent confidence interval [CI], 1.06–1.50; absolute difference, 5.5 percent) and intravenous lidocaine (adjusted RR, 1.21, 95 percent CI, 1.02–1.45; absolute difference, 4.7) but not in recipients of intraosseous amiodarone (adjusted RR, 0.94, 95 percent CI, 0.66–1.32) or intraosseous lidocaine (adjusted RR, 1.03, 95 percent CI, 0.74–1.44).

Results for secondary endpoints, such as survival to hospital admission and survival with favourable neurological function at hospital discharge, also proved to be significantly better when drugs were given intravenously but not intraosseously.

“There were no outcome differences between intravenous and intraosseous placebo, indicating that the access route itself did not demarcate patients with poor prognosis,” the investigators noted.

“Although underpowered for and mitigated by inconclusive evidence for an interaction between the mode of drug delivery and outcome, the consistency of these findings across multiple outcome measures and drugs signals the potential importance of the route of vascular access for drug treatment in OHCA and how this might influence treatment effectiveness,” they added.

As for the mechanisms underlying the differences in outcome between intravenous and intraosseous drug administration during ongoing cardiopulmonary resuscitation (CPR), the investigators pointed out that intraosseous drug delivery may be attenuated by local absorption associated with the physical and chemical characteristics of the drug used. [Crit Care 2016;20:192]

“Unrecognized misplacement of the intraosseous access device could have also contributed to poor drug delivery by this route,” they continued.

“Confirmation of [the ALPS findings] could have an important public health impact, if, as in the present study, it might be found to spare one additional life for every 20 patients treated for shock-refractory OHCA,” they said.