TOXICOLOGY QUESTION OF THE WEEK

May 19, 2023

How do the pharmacokinetics of intraosseous medication compare to those of intravenous?

During the resuscitation of critically ill patients, securing vascular access is crucial. If venous access cannot be secured quickly, intraosseous (IO) cannulation provides a rapid method to deliver medications. The proximal humerus, proximal tibia, distal tibia, and distal femur are all common and appropriate sites for insertion. Sternal IO access can also be obtained with a specialized device. Flow rates through IO catheters vary depending on several factors, including the site of insertion and gauge of the catheter, but rates up to 150 ml/min may be achieved through tibial or humeral IO lines with the pressurized infusion. 

Few studies have been performed measuring the bioavailability of medications administered through IO access compared to intravenous (IV). Much of what we know about IO medication administration is from animal studies and a handful of human studies. From this limited data, time to peak concentration appears to be similar in IO and IV access. One of the few human studies examining IO drug administration compared the delivery of contrast agents via brachial IV and humeral IO during cardiac arrest. This study actually showed a decreased mean time for contrast to reach both the right and left ventricles using humeral IO compared to brachial IV access.  In a separate post hoc analysis of a randomized trial looking at the administration of calcium chloride in cardiac arrest, no difference in ionized calcium levels was found comparing IV and IO administration. While these studies provide some perspective, studying IO pharmacokinetics in clinically relevant subjects remains difficult, as use is typically limited to emergent situations as a fallback after failed IV access.

Several animal models have suggested the possibility of a “depot effect” with some medications. It is thought that some lipophilic drugs may bind to adipose tissue in the medullary cavity, causing slower time to peak concentrations and lower peak concentrations. This depot effect has been demonstrated in porcine models with ceftriaxone, chloramphenicol, phenytoin, vancomycin, and tobramycin. However, it may be somewhat overcome by flushing the catheter after administration.

While IV cannulation remains the preferred mode of access, the use of an IO catheter allows for rapid access in emergencies. Complication rates are low but include extravasation, compartment syndrome, growth plate injury (in pediatrics), and rarely osteomyelitis. At this time, there is insufficient data to suggest altering medication doses for IO administration from IV dosing, and current evidence would not suggest an increased risk for medication toxicity with IO delivery.

REFERENCES:

1. Kenney, C., & Paxton, J. (2022). Intraosseous Catheters. In Emergent Vascular Access: A Guide for Healthcare Professionals (pp. 133–175). essay, SPRINGER NATURE.
2. Buck M, Wiggins B, Sesler JM. Intraosseous drug administration in children and adults during cardiopulmonary resuscitation. Ann Pharmacother. 2007;41(10):1679–86.
3. Cho Y., You Y., Park J.S., et al. Comparison of right and left ventricular enhancement times using a microbubble contrast agent between proximal humeral intraosseous access and brachial intravenous access during cardiopulmonary resuscitation in adults. Resuscitation. 2018; 129: 90-93.
4. Andersen L.W., Holmberg M.J., Granfeldt A., Vallentin M.F. Calcium administration and post-cardiac arrest ionized calcium values according to intraosseous or intravenous administration - A post hoc analysis of a randomized trial. Resuscitation. 2022; 170: 211-212.

Question submitted by Tom Gilmartin, MD. Pediatric Emergency Medicine Fellow, Monroe Carell Jr. Children's Hospital at Vanderbilt.

Comment: This is such an important topic. It is assumed that the pharmacokinetics of IO are the same as IV. Although this intuitively makes sense, there really isn’t much data that demonstrates this is the case. ds

I am interested in any questions you would like addressed in the Question of the Week. Please email me with any suggestions at donna.seger@vumc.org.

DONNA SEGER, MD
Professor Emeritus
Department of Medicine
VUMC