Pre-Hospital Randomized Trial of Medication Route in Out-of-Hospital Cardiac Arrest - PARAMEDIC-3

Nov 06, 2024
Font Size
A
A
A
Author/Summarized by Author:
Amit Saha, MD
Summary Reviewer:
Anthony A. Bavry, MD,MPH,FACC
Trial Sponsor:
National Institute for Health and Care Research
Date Published:
10/31/2024
Date Updated:
11/06/2024
Original Posted Date:
11/06/2024
References

Contribution To Literature:

The PARAMEDIC-3 trial showed that in patients with out-of-hospital cardiac arrest requiring drug administration, an intraosseous-first vascular access strategy did not increase 30-day survival compared with an IV-first strategy.

Description:

The goal of the trial was to compare the efficacy and safety of an initial vascular access strategy of intraosseous (IO) versus peripheral intravenous (IV) access for medication administration in out-of-hospital cardiac arrest.

Study Design

  • Multicenter (United Kingdom)
  • Open-label
  • Randomized

Patients with out-of-hospital cardiac arrest were randomized in a 1:1 fashion in the field by paramedics to initial IO (n = 3,040) or peripheral IV access (n = 3,042). In either group, a vascular access strategy after two failed attempts was at the discretion of the paramedic team. Informed consent for enrollment was obtained following resuscitation from the patient or their legal representative.

  • Total number of enrollees: 6,082
  • Duration of follow-up: 6 months
  • Mean patient age: 68 years
  • Percentage female: 35%

Inclusion criteria:

  • Age ≥18 years
  • Out-of-hospital cardiac arrest undergoing cardiopulmonary resuscitation (CPR)
  • Need for vascular access to administer cardiac arrest medications

Exclusion criteria:

  • Known or apparent pregnancy
  • Established vascular access

Other salient features/characteristics:

  • Initial shockable rhythm: 20%
  • Median number of shocks: 3
  • Median cumulative epinephrine dose: 5 mg
  • Witnessed cardiac arrest: 63%
  • Bystander CPR performed: 70%
  • Public access defibrillator used: 8%
  • IO access via proximal tibia: 78%

Principal Findings:

The primary outcome, 30-day survival for IO vs. IV, was: 4.5% vs. 5.1%, odds ratio (OR) 0.94 (95% confidence interval [CI] 0.68-1.32), p = 0.74.

Secondary outcomes for IO vs. IV:

  • Return of spontaneous circulation (ROSC) at any time: 36.0% vs. 39.1%, OR 0.86 (95% CI 0.76-0.97)
  • Sustained ROSC at hospital handover: 21.7% vs. 24.6%, OR 0.85 (95% CI 0.74-0.98)
  • Modified Rankin scale (mRS) score ≤3 among survivors at hospital discharge: 2.7% vs. 2.8%, OR 0.91 (95% CI 0.57-1.47)

Vascular access characteristics for IO vs. IV:

  • Median time from emergency call to vascular access: 21 vs. 22 minutes
  • Median time from emergency call to epinephrine administration: 24 vs. 24 minutes
  • First successful vascular access according to assigned treatment strategy: 94.4% vs. 64.6%
  • Serious adverse events related to vascular access: 0% vs. 0%

Interpretation:

Observational data suggesting worse clinical outcomes in out-of-hospital cardiac arrest managed with IO access are confounded by its frequent role as a second-line intervention when peripheral IV access fails. Recently, the VICTOR trial of patients in Taiwan demonstrated no improvement in survival to discharge with a primary IO vs. IV access strategy. The current study similarly failed to demonstrate a survival benefit to up-front IO vascular access at 30 days.

The PARAMEDIC-3 study was limited by slow enrollment and ultimately included only 41% of the intended sample size before termination, although treatment effect estimates suggested a low likelihood of achieving the primary outcome with full enrollment. There was significant crossover to IO access, including almost 20% of the entire IV arm who did not undergo two full attempts at IV access first. These protocol violations may have biased the results toward the null. Frequencies of any and sustained ROSC were slightly lower with IO access, which the investigators posit may relate to delayed time to peak drug concentration in animal models of tibial IO access. This was not observed, however, in the primary endpoint of the simultaneously published IVIO trial, and may have been due to chance as an exploratory outcome. These complementary trials therefore corroborate prior data to suggest no specific advantage to an initial IO access strategy in out-of-hospital cardiac arrest.

References:

Couper K, Ji C, Deakin CD, et al., for the PARAMEDIC-3 Collaborators. A Randomized Trial of Drug Route in Out-of-Hospital Cardiac Arrest. N Engl J Med 2024;Oct 31:[Epub ahead of print].

Nielsen N. Editorial: The Way to a Patient’s Heart — Vascular Access in Cardiac Arrest. N Engl J Med 2024;Oct 31:[Epub ahead of print].

Clinical Topics: Arrhythmias and Clinical EP, Cardiovascular Care Team, SCD/Ventricular Arrhythmias, Vascular Medicine

Keywords: Drug Administration Routes, Emergency Medical Technicians, Out-of-Hospital Cardiac Arrest, Vascular Access Devices


< Back to Listings