83: Pharmacodynamics of fluid challenge, why is epinephrine added to lidocaine for injections, and a resource to stay up to date with FDA medwatch alerts

In this episode I’ll:

1. Discuss an article on the pharmacodynamics of a fluid challenge.
2. Answer the drug information question “Why is epinephrine added to lidocaine for injection?”
3. Share a resource for staying up to date with FDA safety information.
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Article

Pharmacodynamic Analysis of a Fluid Challenge

Lead author: Hollmann Aya
Published in Critical Care Medicine May 2016

Background

Earlier in my career I didn’t pay close attention to IV fluids. As I discussed in episode 42 on the treatment of sepsis and septic shock:

Despite a lack of focus on IV fluids in my training, I’ve learned to treat them as a medication that requires a specific dose to be effective.

So of course the title of this article “Pharmacodynamic Analysis of a Fluid Challenge” caught my eye.

The authors of the study perfectly summarize the fluid challenge by saying:

The administration of IV fluids is essential for the management of critically ill patients. To reduce any undesirable effects from the inappropriate use of fluids , the fluid challenge technique has been recommended and it is one of the commonest interventions in intensive care. A fluid challenge is a test in which a small bolus of IV fluid is given over a short period of time to assess hemodynamic response and it is considered as the “gold standard” test for assessment of fluid responsiveness.

Purpose

The study was performed to describe the pharmacodynamics of a fluid challenge over a 10-minute period in postoperative patients.

Methods

The study was a prospective observational study in 26 postoperative general and cardiothoracic ICU patients. A 250 mL fluid challenge was performed over 5 minutes. Data were recorded over 10 minutes after the end of fluid infusion.

Results

The predicted maximal effect on cardiac output was observed at 1.2 minutes (95% credible interval, –0.6 to 2.8 min) in responders. After 10 minutes, there was no evidence of a difference between responders and nonresponders for any hemodynamic variable.

Conclusion

The authors concluded:

The maximal change in cardiac output should be assessed 1 minute after the end of the fluid infusion….The effect of a fluid challenge on hemodynamics is dissipated in 10 minutes similarly in both groups [responders and nonresponders].

Drug information question

Q: Why is epinephrine added to lidocaine for injection?

When this question came up, my colleagues were debating whether the purpose of adding epinephrine to lidocaine was to reduce bleeding or prolong the effects of lidocaine.

A: To prolong the effects of lidocaine.

Here is what we found from a 2003 study in rats published in Anesthesiology:

Adding epinephrine to lidocaine solutions increases the intensity and duration of sciatic nerve block in the rat. The early increase in intensity is not matched with an increase in intraneural lidocaine content at these early times, although the prolonged duration of block by epinephrine appears to correspond to an enlarged lidocaine content in nerve at later times, as if a very slowly emptying “effector compartment” received a larger share of the dose. The increase in early analgesia without increased lidocaine content may be explained by a pharmacodynamic action of epinephrine that transiently enhances lidocaine’s potency, but also by a pharmacokinetic effect that alters the distribution of the same net content of lidocaine within the nerve.

Resource

To stay up to date with medication safety warnings from the FDA, I subscribe to their Medwatch alerts. Before doing this, providers and patients would often ask me questions based on news articles describing recent FDA safety warnings and I would be in the dark about it. Now I receive the safety information at the same time as the media, so I am no longer caught off guard with such questions.

The FDA offers dozens of different alerts. When you sign up be sure to do so only for alerts that are relevant to you, lest you get “FDA alert fatigue” in your inbox.

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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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