1. Discuss an article about therapeutic drug monitoring of voriconazole.
2. Answer the drug information question “When alteplase is given for massive PE in a patient undergoing cardiopulmonary resuscitation, how long should CPR be continued?”
3. Share one of my top resources for keeping up to date with medical literature.
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My book A Pharmacist’s Guide to Inpatient Medical Emergencies is now available in Amazon. Ever since I joined my hospital medical emergency team, I’ve been passionate about teaching other pharmacists how they can make a difference in patient outcomes by being part of the code team.
Episode 1 of this podcast was about how fewer patients die in the hospital when pharmacists are members of the cardiopulmonary resuscitation team. Now on the 1 year anniversary of The Elective Rotation Podcast I am excited to make this book available for other pharmacists to learn and refine the clinical skill of responding to inpatient medical emergencies. You can find a link to the book in amazon at clinicalpharmacybooks.com.
Article Risk Factors for Voriconazole-Associated Hepatotoxicity in Patients in the Intensive Care Unit
Lead Author: Yan Wang
Published in: Pharmacotherapy Early Access July 2016
Background
When voriconazole cannot be administered due to hepatotoxicity, for infections such as invasive aspergillosis, salvage therapy with more toxic medications such as amphotericin is required.
Purpose
The authors sought to identify risk factors for voriconazole-associated hepatotoxicity and to report the incidence of hepatotoxicity in critically ill patients receiving voriconazole.
Methods The study was a prospective observational study in a single ICU in China. The study included 63 adult ICU patients who had a length of stay longer than 3 days, received voriconazole treatment for at least 3 days, and had at least one voriconazole trough level. All patients received CYP2C19 genotyping. Liver function testing was performed before, during, and after voriconazole therapy.
Results
Hepatotoxicity occurred in 12 of the 63 patients. Multivariate Cox regression analysis demonstrated that hepatotoxicity was independently associated with voriconazole trough. There was a significant difference between patients with voriconazole trough levels of 4 mg/L or higher and those with voriconazole trough levels lower than 4 mg/L.
Conclusion
The authors concluded that voriconazole trough:
was an independent risk factor associated with a greater risk of developing hepatotoxicity in critically ill patients, with a potentially toxic target trough concentration threshold of 4 mg/L identified for this complex population.
Discussion
The ability to predict and avoid hepatotoxicity from voriconazole has significant implications for the care of adult ICU patients on voriconazole. References such as Johns Hopkins Antibiotic Guide already identify voriconazole levels < 1 mg/L with treatment failure, and > 5.5 mg/L with encephalopathy. As a single center study, it will be helpful for the results to be confirmed. Until then it seems reasonable to attempt to keep voriconazole trough levels therapeutic, but under 4 mg/L.
Drug information question
Shout out to “Pharmacy Andrew” for posing this question in the Pharmacy Nation slack group:
Q: When alteplase is given for massive PE in a patient undergoing cardiopulmonary resuscitation, how long should CPR be continued?
A: ??? I don’t know that this question has a definitive answer.
One reference from episode 17 on IV push tPA appeared to be split evenly between a time of 15 minutes vs 90 minutes but exactly how long each patient received CPR was not clear. “Pharmacy Z” posted an article that suggested CPR be continued for 15 minutes or longer depending on the judgment of the team. Finally, “Pharmacy Chris” presented a case where 15-20 minutes after IV push alteplase for PE, a patient achieved ROSC. This sounds like a topic that would be worth discussing ahead of time with your critical care team to ensure everyone is on the same page. Based on what I’ve seen on this topic so far, I’d suggest waiting a minimum of 15 minutes after IV alteplase in a code before considering whether CPR should continue.
Resource
The resource for this episode is one of my key professional resources that I use to stay up to date with medical literature: Pharmacist’s Letter. I’ve been a subscriber of Pharmacist’s Letter since 2002. I trust their advice to be relevant, current, and unbiased. One of the challenges of a hospital-based pharmacist is keeping up with new medications/indications in the community setting. I know that when I read the monthly Pharmacist’s Letter, I’ll be on top of major developments in both community and hospital pharmacy. Pharmacist’s Letter has given me a link to share for a 30 day free trial of their product. If you sign up for the trial using my link, Pharmacist’s Letter will compensate me with a $5 gift card. I hope you find Pharmacist’s Letter as helpful as I do!
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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