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PARAMEDIC-3 Trial: Drug Route in OHCA

Nov 07, 2024

In response to the uncertainty of which route is better for drug administration in Out-of-Hospital Cardiac Arrest (OHCA) ie., intraosseous (I/O) or intravenous (IV), "we conducted the PARAMEDIC-3 trial to determine the clinical effectiveness of an intraosseous-first strategy, as compared with an intravenous-first strategy, in adults with out-of- hospital cardiac arrest."

Bottom Line

Survival at 30 days was 4.5% (137/3030) (I/O) vs 5.1% (155/3034) in IV group (adjusted odds ratio, 0.94; 95% confidence interval [CI], 0.68 to 1.32; P=0.74) ie., I/O did not increase 30 day survival over IV.

The Study

Couper K et al. A Randomised Trial of Drug Route in Out-of-Hospital Cardiac Arrest. NEJM October 31st 2024(1)

What They Did

This was an open label, pragmatic, randomised trial, conducted in the United Kingdom.

Inclusion Criteria:

≥18 years of age and requiring vascular access for drug administration during cardiopulmonary resuscitation.
Medical causes of cardiac arrest

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Bottom Line

The Study

Couper K et al. A Randomised Trial of Drug Route in Out-of-Hospital Cardiac Arrest. NEJM October 31st 2024(1)

What They Did

This was an open label, pragmatic, randomised trial, conducted in the United Kingdom.

Inclusion Criteria:

≥18 years of age and requiring vascular access for drug administration during cardiopulmonary resuscitation.
Medical causes of cardiac arrest comprised 81.6% of cases. other causes included trauma, overdose, electrocution and 11.8% had missing data.

Exclusion Criteria included a known or apparent pregnancy.

Randomisation

Patients requiring vascular access during resuscitation, were randomly assigned in a 1:1 ratio (sealed in sequentially numbered, tamper-proof, opaque envelopes), to receive

Intraosseous access or
Intravenous access.

If it was not possible to achieve the vascular access initially assigned, within two attempts, the route used for subsequent attempts was then chosen by the treating paramedic.

Primary Outcome

Survival at 30 days.

Secondary Outcomes

Return of spontaneous circulation (ROSC) after randomization
- Including time to return of spontaneous circulation
Sustained ROSC at the time of transfer of care to the receiving hospital
Survival at hospital discharge
Survival at 3 months, and 6 months
Hospital Length of stay
Neurologic function (modified Rankin scale) at discharge
- at 3 and 6 months;
Health-related quality of life (EuroQol 5-Dimension 5-Level [EQ-5D-5L] questionnaire)
- at 3 and 6 months.

N= 6096: 3030 patients in the I/O group and 3034 patients in the IV group.
It was estimated that a sample size of 14,972 patients would provide 90% power to detect a difference of 1 percentage point (3.2% vs. 4.2%) in 30-day survival between the intraosseous group and intravenous group. Due to the slow nature of recruitment, it was stopped at the end of the funded recruitment period, when 6096 participants had been recruited and before the second formal interim analysis was performed.

What They Found

Primary Outcome

Survival at 30 days was 4.5% (137/3030) (I/O) vs 5.1% (155/3034) in IV group (adjusted odds ratio, 0.94; 95% confidence interval [CI], 0.68 to 1.32; P=0.74)

Secondary Outcomes

There was no significant increase in 30 day survival from OHCA when I/O was used compared to IV access.Return of spontaneous circulation (ROSC) was lower in the I/O group
- 36% (1092/3031) in the I/O group and 39.1% (1186/3035) patients (39.1%) in the IV group (adjusted odds ratio, 0.86; 95% CI, 0.76 to 0.97)
Sustained ROSC was also lower in the I/O group 21.7% vs 24.6% at the time of transfer of care to the receiving hospital
Survival at hospital discharge was similar in both groups.
- 2.7% (80/2994) in I/O group vs 2.8% (85/2986) in theIV group (adjusted odds ratio, 0.91; 95% CI, 0.57 to 1.47).
Median Time from arrival on the scene to vascular access was 12 minutes in both groups
Median time from arrival on the scene to drug administration was 14 minutes in the I/O group and 15 minutes in the IV group.
Bystander CPR was performed in 68.7% of patients receiving I/O access and 70.5% of those receiving IV access.
A shockable rhythm was present in 18.6% of those receiving I/I access and 20.8% of those receiving IV access.

My Take on This

I/O versus IV is an important discussion as it not only relates to OHCA, but to our ability to obtain IV access, in hospital during an arrest.

A few important points to raise about this study:

The sample size was changed during the study, so that less than 50% of the original sample size was used. This was a practical decision related to funding. However it does affect the original power calculations.
The quality of resuscitation was not reviewed, nor was the hospital-based care that patients received.
We aren't sure if there is some bias involved here as there were exclusions from randomisation in patients with a pre-existing vascular access. We have no information on why access had been established.

This study showed that the use of an I/O-first strategy did not result in higher 30-day survival than an IV-first strategy. The rate of ROSC was lower in those patients with I/O access. However, It would be a one try for IV, then fo to I/O. This is not the patient to be bringing the ultrasound to the bedside for.

I wouldn't change my current practice of establishing IV access first. However, this conclusion is far too simplistic. There are so many more factors involved which include:

Is this a shockable/non-shockable rhythm cardiac arrest?
- In shockable rhythms, we have a little more time as adrenaline early is shown to produce worse outcomes.
The location of the I/O for giving medications is important. HUmeral head is far better at delivering drugs to the heart, than lower extremity I/Os.

My current practice is one go at IV, if not in in the cardiac arrest patient then I/O rapidly so we can give what is needed and an IV access may be attempted concurrently.

References

Couper K et al. A Randomised Trial of Drug Route in Out-of-Hospital Cardiac Arrest. NEJM October 31st 2024
Daya M.R et al. Survival After Intravenous Versus Intraosseous Amiodarone, Lidocaine, or Placebo in Out-of Hospital Shock-Refractory Cardiac Arrest. Circulation 2020;141:pp 188–198. DOI: 10.1161