Episode 191: Effects of IV push administration on beta-lactam pharmacodynamics, duration of octreotide in variceal bleeding, and a video based resource

In this episode I’ll:

1. Discuss an article about the effects of IV push administration on beta-lactam pharmacodynamics.
2. Answer the drug information question “How long should octreotide be continued in patients with variceal bleeding?”
3. Share a video-based resource that explains complex ICU topics to patients and students.

 

Article

Effects of i.v. push administration on β-lactam pharmacodynamics

Lead author: Jill M. Butterfield-Cowper

Published in American Journal of Health-System Pharmacy May 2017

Background

IV push administration of antibiotics has several potential benefits over IV minibag administration. Supply costs are less due to not needing extra IV bags or tubing. The administration time is much shorter – 5 minutes or less compared to 30 minutes or more with an IV minibag.

Beta-lactam antibiotics exhibit time above minimum inhibitory concentration (MIC) killing effects. Shortening the administration time has the potential to negatively impact the time above MIC. The authors of this study examined the effects of IV push administration on the time above MIC exposures of meropenem, cefepime, and aztreonam.

Methods

In this study, previously published pharmacokinetic data for meropenem, cefepime, and aztreonam was used. The authors used Monte Carlo simulations of 30-minute and 5-minute infusions to assess the probability of attaining appropriate time above MIC for each antibiotic.

Both FDA approved and common alternative dosing regimens were studied. This included 500 mg every 6 hours and 1 g every 8 hours for meropenem, 1 g every 6 hours and 2 g every 8 hours for cefepime, and 2 g every 8 hours for aztreonam. For each regimen examined, means and standard deviations for the percentage of the dosing interval that the free drug concentration remained above the MIC were calculated and reported.

Results

The authors noted no to minor differences between 30-minute and 5-minute infusions for most dosing regimens. The two largest differences in favor of the 30-minute infusion were for a MIC of 4 mcg/mL for meropenem 500 mg every 6 hours (8% difference) and MIC of 16 mcg/mL for aztreonam (12% difference).

Conclusion

The authors concluded:

Simulations of meropenem, cefepime, and aztreonam by i.v. push over 5 minutes indicated that there would be minimal or no effect on pharmacodynamic exposures compared with the effect when administered by 30-minute infusions.

 

Discussion

The results of this analysis demonstrate that pharmacodynamics of meropenem, cefepime, and aztreonam is not significantly altered by giving them via IV push. Clinical efficacy was not compared, and because it was a Monte Carlo analysis of preexisting data, there is no way to determine whether the rate of adverse effects between groups would be different.

The results of this study remove the concern of pharmacodynamic disadvantages to IV push administration of meropenem, cefepime, and aztreonam. However, the major barrier to adoption of IV push antibiotics remains – 5 minutes is longer than seems reasonable for IV push administration. I would like to see studies examining the rate of adverse effects with IV push antibiotics over 1 or 2 minutes.

Drug information question

Q: How long should octreotide be continued in patients with variceal bleeding?

A: 5 days

When given to patients with variceal bleeding, octreotide helps achieve hemostasis and prevent rebleeding. Two studies that demonstrated the benefits of octreotide in variceal bleeding used a 5-day duration. In the European Acute Bleeding Oesophageal Variceal Episodes (ABOVE) trial at the end of 5 days, active bleeding from esophageal varices was less frequent in the octreotide group.

In another study published in NEJM in 1995 after five days, the proportion of patients who had survived without rebleeding was higher in the octreotide group.

Resource

The resource for this episode is the Demystifying Medicine Youtube Channel. This channel is the result of a cross-disciplinary course at McMaster University and has been active since 2013. Their main task is to generate educational content in the form of short presentations, animations, interviews, skits or by other creative ways that may help increase the understanding of complex clinical and biomedical material. The channel has several interesting videos on sepsis, post-intensive care syndrome, as well as many other topics. The videos are geared toward the education of patients or students in the beginning years of their study.

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If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.

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