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Volume 26, Issue 1, Pages 31-38 (January 2008)


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Does intraosseous equal intravenous? A pharmacokinetic study☆☆

Daniel D. Von Hoff, MD, FACPa, John G. Kuhn, Pharm D, FCCP, BCOPb, Howard A. Burris III, MD, FACPc, Larry J. Miller, MDdCorresponding Author Informationemail address

Received 28 September 2006; received in revised form 20 March 2007; accepted 21 March 2007.

Abstract 

Study Objective

Despite the growing popularity of intraosseous infusion for adults in emergency medicine, to date there has been little research on the pharmacokinetics of intraosseously administered medications in humans. The objective of the study was to compare the pharmacokinetics of intraosseous vs intravenous administration of morphine sulfate in adults.

Methods

The study followed a prospective, randomized, crossover design. Each subject was equipped with an indwelling intraosseous access device and an intravenous line. Subjects were randomized to receive a 5-mg bolus of morphine sulfate infused intraosseously or intravenously, followed by the alternate administration route 24 hours later.

Serial venous blood samples (5 mL) were taken at baseline and at 13 time points over 8 hours postinfusion. Blood samples were analyzed for morphine concentration by radioimmunoassay. Pharmacokinetic parameters were calculated from the data, including maximum plasma concentration (Cmax), time to maximum concentration (Tmax), and area under plasma concentration-time curve (AUC), among others. Data were analyzed by analysis of variance.

Results

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 (P = .0247), which in the opinion of the investigators was thought to be due to a minor deposition effect near the intraosseous port or in the bone marrow.

Conclusion

The results support the bioequivalence of intraosseous and intravenous administration of morphine sulfate in adults.

a Translational Genomics Research Institute and Arizona Cancer Center, University of Arizona, Phoenix, AZ 85721, USA

b University of Texas Health Science Center at San Antonio, San Antonio, TX 78249, USA

c Centennial Medical Center, Nashville, TN 37203, USA

d Vidacare Corporation, San Antonio, TX 78216, USA

Corresponding Author InformationCorresponding author. Tel.: +1 210 375 8500; fax: +1 210 375 8537.

 Presentation Information: The study was presented at the National Association of Emergency Medical Services Physicians annual meeting in Naples, FL, January 2005.

 Funding/Financial Interest: The study was funded by a grant from LifeQuest Medical. At the time of the study, Larry Miller was the CEO of LifeQuest Medical. Doctor Kuhn and Dr Von Hoff were shareholders of LifeQuest Medical. Doctor Burris was principal investigator.

☆☆ Author Contribution Statement: D. V. H. and J. K. conceived the study, designed the trial, and supervised conduct of the trial. D. V. H., J. K., and L. M. supervised the data collection. H. B. III, D. V. H., and J. K. were responsible for recruitment of participating centers and patients. The study nurse at LifeQuest Medical managed the data, including quality control. D. V. H. and J. K. drafted the manuscript, and L. M. contributed substantially to the revision, adding the implications for emergency medicine and prehospital emergency care. J. K. takes responsibility for the article as a whole.

PII: S0735-6757(07)00218-5

doi:10.1016/j.ajem.2007.03.024


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