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Three Part Question

In [patients requiring intraosseous drug administration], does the [use of an intraosseous route] lead to [any changes in systemic absorption compared to an intravenous route]?

Clinical Scenario

A 30 year-old male is brought in by paramedics with ongoing generalised tonic/clonic seizures that have been ongoing for 25 minutes. The paramedics have given 15mg of Midazalam IM with no effect, and couldn't gain IV access due to extensive track marks over the patient’s veins from extensive IV drug use.

Vascular access is urgently needed to terminate this state of status epilepticus and to prevent further neurological sequelae. A central line would take too long to place, and would be extremely difficult in this patient. You decide to use an IO access kit to gain rapid access in this patient, so that benzodiazepines can be administered.

Search Strategy

MEDLINE(R) 1946 to August Week 2 2014 using the OVID interface.
[exp Infusions, Intraosseous/ or intraosseous.mp.] AND [exp Absorption/ or absorption.mp. OR pharmacokinetics.mp. or exp Pharmacokinetics/] LIMIT to [english AND humans]

Search Outcome

A search of Medline produced only 22 papers, of which 5 were of relevance to this question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Von Hoff, D. D. Kuhn, J. G. Burris, H. A., 3rd Miller, L. J. January 2008 USA	25 Adults with a diagnosis of cancer in need of opiate based pain relief, in whom IV access had failed (defined as vein inaccessibility, clotting of the vein or intravenous line, infection, or extravasation necrosis around the intravenous line).	IO vs IV administration of morphine sulphate in adult cancer patients.	Efficacy of IO administration of morphine compared to IV administration	No statistically significant differences were observed between intraosseous and intravenous administration of morphine sulfate for nearly all of the pharmacokinetic parameters including Cmax (235 ± 107 vs 289 ± 197 ng/mL, mean ± SD, IO vs IV, respectively), Tmax (1.3 ± 0.5 vs 1.4 ± 0.5 minutes), and AUC(0-∞) (4372 ± 1785 vs 4410 ± 1930 ng min−1 mL−1). There was, however, a statistically significant difference in the volume of distribution in the central compartment, Vd	The IO device was implanted in the iliac crest, which is not commonly used for IO access in the ED. The device was a surgically inserted IO port, rather than an IO needle, and thus may offer different administration pharmacokinetics than a needle.

Comment(s)

This is a well written paper that looks at 25 adult cancer patients who have been administered morphine sulphate via an IO port vs an IV catheter. This was a latin square cross over trial, where the patients acted as their own controls, eliminating the potential confounding factor of differences in patient metabolism of drugs. There is little evidence available on the pharmacokinetics and absorption profiles of different drugs that are given by the IO route. Although there does appear to be a solid base of literature demonstrating the equivalence to IV administration of hydrophilic drugs, there is less evidence on the administration of hydrophobic drugs. The concern there is that the main IO access points in adults (e.g. proximal tibia) contain mostly yellow marrow, which is 95% fat cells. It is possible that administration of hydrophobic drugs via an IO could lead to a delay in systemic absorption due to the drug being taken up into the fatty tissue of the bone marrow. There were a few papers in animal models that demonstrated the efficacy of IO access for some lipophilic drugs such as midazolam, and these showed that there was some evidence of a depot forming, but that clinically this made little difference.

Clinical Bottom Line

IO access is suitable for administration of medication, and is clinically equivalent to the IV route for both hydrophilic and hydrophobic drugs based on current evidence.

References

1. Von Hoff, D. D. Kuhn, J. G. Burris, H. A., 3rd Miller, L. J. Does intraosseous equal intravenous? A pharmacokinetic study American Journal of Emergency Medicine