Acute Effects of a Single Dose of Chemotherapeutic Agents Delivered to Swine through the Intraosseous Route

The development and complexity associated with polychemotherapeutic protocols has increased the importance and the need for reliable vascular access. This study was designed to determine the safety of 3 different chemotherapeutic drugs delivered via the intraosseous tibial route in a swine model.

Each of 4 groups of immature Yorkshire swine received different chemotherapeutic protocols which consisted of infusing known vesicants: Group 1-Mitomycin (n=6); Group 2-CHOP (comprising cyclophosphamide, doxorubicine hydrochloride, Oncovin, and prednisolone, (n=6); Group 3-Adriamycin standard dose (n=6); and Group 4-Adriamycin at different doses (n=3). For Groups 1–3, we investigated the effects of the standard maximum-allowed dose of drug delivered via the IO tibial route in swine (using the EZ-IO system, Vidacare Corporation, Shavano Park, TX). For Group 4, in one animal each, we investigated the effects of Adriamycin delivered via the IO tibial route at double maximum dose, maximum dose without a post-drug flush, and drug delivered with increased infusion pressure. As a control in all animals, normal saline was infused through the contra-lateral tibia. Animals were monitored for 7 days, followed by necropsy and histological analysis of the infused bone.

In the Mitomycin group, similar effects on marrow cells and bone spicules between the saline infused controls and the drug infused histology samples in half the group (n=3) were detected. In the other half of the group (n=3) there was a trend toward more loss of marrow cells and bone spicules in the drug infused limb. There were no differences in morphological changes between the drug infused limb and the saline control limb (p=.61). The CHOP infusion showed a trend toward loss of marrow cells, bone spicules, and some focal hemorrhage in the histology samples from the drug infused limb. Marrow cell loss was greater in the drug-infused limb (p<0.05). Adriamycin infusion caused significant morphological changes in the drug-infused limb (p<.05). For the Adriamycin/no flush protocol there was a reduction in marrow cells and loss of bone spicules in a focused area in the drug infused limb. Double-dose Adriamycin seemed to reduce marrow cells and bone spicules to the low normal range. Adriamycin high-pressure drug delivery caused a slight reduction of marrow cells and bone spicules. However, there were changes in tissue morphology at the injection site indicated by loss of bone marrow cells, and/or bone spicules, and focal hemorrhage represented by blood in the field. All changes detected were considered mild and not unexpected. There were no cases of osteomyelitis, significant necrosis of bone, or fat necrosis detected in the marrow samples.

In this limited study, it appears that the IO route of infusing chemotherapy agents could be a safe alternative to IV infusion. Longer term studies are needed to more fully characterize the safety of IO delivery of chemotherapeutic agents.

Hoskins:Vidacare Corporation: Research Funding. Philbeck:Vidacare Corporation: Employment. Miller:Vidacare Corporation: Employment, Equity Ownership. Kramer:Vidacare Corporation: Consultancy, Patents & Royalties, Research Funding.