What alternative routes can be used for drug administration during cardiopulmonary resuscitation when intravenous (IV) and intra‑osseous (IO) access are unavailable?

Endotracheal Route is the Primary Alternative When IV/IO Access is Unavailable

When intravenous and intraosseous access cannot be established during CPR, the endotracheal route is the recommended alternative for administering lipid-soluble resuscitation drugs, though it is significantly less effective than vascular routes. 1

Endotracheal Drug Administration: The Only Viable Alternative

Which Drugs Can Be Given Endotracheally

The American Heart Association identifies only four medications that can be administered via endotracheal tube, remembered by the mnemonic "LEAN": 1

• Lidocaine
• Epinephrine
• Atropine
• Naloxone

These are the only lipid-soluble drugs with documented absorption through the tracheal mucosa during CPR. 1

Critical Dosing Differences for Endotracheal Route

The endotracheal dose must be significantly higher than the IV/IO dose because absorption is unpredictable and incomplete. 1

• Epinephrine endotracheal dose: 0.1 mg/kg (10 times the IV/IO dose of 0.01 mg/kg) 1
• Atropine endotracheal dose: 0.04-0.06 mg/kg (2-3 times the IV/IO dose of 0.02 mg/kg) 1
• The standard IV dose should be diluted in 3-5 mL of normal saline and instilled as deeply as possible into the endotracheal tube 2

Major Limitations of Endotracheal Administration

The endotracheal route has substantial disadvantages that make it inferior to any vascular access: 1

• Drug absorption is unreliable and highly variable - effects may not be uniform compared to IV administration 1
• Lower peak drug concentrations are achieved compared to vascular routes 2
• Delayed onset of action due to unpredictable absorption 1
• Requires interruption of ventilation for drug instillation 2
• European guidelines express "doubts about the reliability of this route" and state that "intravenous access is preferable" 1

Why Other Routes Are Not Alternatives During CPR

Central Venous Access: Not Feasible During Active Resuscitation

Central venous catheter placement is explicitly not recommended as an initial route during cardiac arrest because: 1

• Placement is time-consuming and requires significant training 1
• Interrupts chest compressions, which is unacceptable during CPR 3
• The procedure complexity makes it impractical during active resuscitation 1

Intramuscular Route: Ineffective During Cardiac Arrest

IM administration is contraindicated during CPR because: 4

• Peripheral circulation is essentially absent during cardiac arrest, preventing drug absorption 4
• Does not allow medication titration 4
• Causes unnecessary pain without therapeutic benefit 4

Clinical Algorithm for Drug Administration During CPR

Follow this hierarchical approach: 1, 5

1. First priority: Attempt peripheral IV access (but limit attempts to avoid delaying resuscitation) 1

   • If successful, follow each medication with 20 mL saline flush and briefly elevate the extremity 3

2. Second priority: Establish IO access immediately if IV fails or is not feasible 1

   • Humeral or sternal sites preferred over tibial for faster drug delivery 3
   • Do not waste time with prolonged IV attempts 3

3. Last resort only: Endotracheal administration if vascular access is impossible 1

   • Use 10x dose for epinephrine, 2-3x dose for atropine 1
   • Instill deeply into the endotracheal tube 2
   • Only use for LEAN medications 1

Critical Pitfalls to Avoid

• Never delay resuscitation attempting prolonged IV access - switch to IO after 1-2 failed attempts 3, 5
• Never use standard IV doses for endotracheal administration - this will result in subtherapeutic drug levels 1
• Never assume endotracheal administration is equivalent to vascular routes - one pediatric study showed similar outcomes, but the route remains unreliable 1
• Never forget the saline flush when using peripheral IV during CPR - drugs may not reach central circulation without it 3
• Do not use IM or subcutaneous routes during cardiac arrest - there is no peripheral perfusion to enable absorption 4

Evidence Quality Note

While one pediatric study demonstrated similar ROSC and survival rates regardless of IV versus endotracheal administration method 1, the overall evidence strongly favors vascular access when possible. The endotracheal route should be viewed as a compromise measure only when all vascular access options have been exhausted. 1