Why does intravenous (IV) access have better outcomes than intraosseous (IO) access for medication administration during cardiopulmonary resuscitation (CPR) in cardiac arrest patients?

Why IV Access Achieves Better Outcomes Than IO Access During CPR

The most recent high-quality evidence from 2025 shows no significant difference in survival or neurological outcomes between IV and IO access during cardiac arrest, contradicting earlier observational data that suggested IV superiority. 1, 2

Current Evidence Hierarchy

The 2025 IVIO randomized controlled trial—the largest and most rigorous study to date—found no significant difference between initial IO versus IV access for:

• Sustained return of spontaneous circulation (30% IO vs 29% IV, p=0.49) 1
• 30-day survival (12% IO vs 10% IV) 1
• Favorable neurological outcomes at 30 days (9% IO vs 8% IV) 1

A concurrent 2025 meta-analysis of three RCTs (9,293 patients) confirmed these findings, showing no significant differences in any outcome measure between routes 2.

Why Earlier Guidelines Suggested IV Superiority

Pharmacokinetic Advantages of Central Circulation

The 2020 International Consensus guidelines noted that observational studies showed point estimates generally favoring IV over IO access, though these differences were not statistically significant in adequately powered analyses 3. The theoretical advantages of IV access include:

• Higher peak drug concentrations: Central venous administration achieves higher peak concentrations and shorter circulation times compared to peripheral routes 3
• Faster drug delivery to central circulation: Peripheral IV drugs reach central circulation more predictably when followed by 20-mL saline flush and brief extremity elevation 3, 4

Site-Specific IO Performance Issues

Animal studies revealed significant pharmacokinetic differences between IO sites:

• Tibial IO is slower: Peak arterial concentrations occurred at 107±27 seconds for tibial IO versus 53±11 seconds for sternal IO 5
• Tibial IO delivers less drug: Only 65% of the intended dose reached circulation via tibial IO compared to sternal IO 5
• Sternal IO approaches IV performance: Time to peak concentration was similar between sternal IO (97±17 seconds) and central venous access (70±12 seconds) 5

Current Guideline Recommendations

The 2020 International Consensus guidelines suggest attempting IV access first, but recommend IO access if IV attempts are unsuccessful or IV access is not feasible (weak recommendation, very low-certainty evidence). 3

The American Heart Association states it is reasonable to establish IO access if IV access is not readily available 3. Both routes are considered acceptable, with the choice depending on:

• Provider skill and experience 3
• Speed of access establishment (IO success rate 92% vs IV 80% on first two attempts) 1
• Clinical context (in-hospital patients often have existing IV access) 3

Critical Practical Considerations

Why Observational Data May Have Been Misleading

The 2020 guidelines acknowledged that patients requiring IO access likely represent a sicker population with more difficult vascular access, creating unmeasured confounding in observational studies 3. This selection bias may have artificially inflated apparent IV superiority.

Optimal IO Technique

When IO access is used:

• Humeral or sternal sites are preferred over tibial for faster drug delivery and higher bioavailability 5
• Commercially available automated devices facilitate rapid placement 3, 6
• IO provides access to a noncollapsible venous plexus, maintaining reliability during low-flow states 3

Optimal IV Technique

When peripheral IV access is used:

• Always follow medications with 20-mL saline flush to facilitate central circulation delivery 3, 4
• Briefly elevate the extremity during and after administration 3, 4
• Use the largest, most proximal vein available 3

Common Pitfalls to Avoid

• Do not delay resuscitation attempting prolonged IV access: If IV cannot be rapidly obtained, establish IO access immediately rather than wasting time on multiple failed IV attempts 3, 6
• Do not assume all IO sites perform equally: Tibial IO is significantly inferior to humeral or sternal sites 5
• Do not skip the saline flush: Peripheral IV drugs without adequate flush may not reach central circulation effectively 3, 4
• Do not interrupt chest compressions: Vascular access should be established without interrupting CPR 3