In this episode I’ll:
1. Discuss an article about the effects of continuous renal replacement therapy on linezolid.
2. Answer the drug information question “Should insulin detemir be given once or twice daily?”
3. Share a resource for researching the hepatotoxicity potential of a given medication.
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Article
Lead author: Gianluca Villa
Published in Critical Care November 2016
Background
Continuous renal replacement therapy (CRRT) has the potential to dramatically alter pharmacokinetic and pharmacodynamic properties of antibiotics in critically ill patients.
There are many different forms of CRRT, and not all antibiotics have been well-studied to determine how they are affected.
In episode 13 I gave some general rules (and exceptions to the rules) to follow when adjusting antibiotic dosing in CRRT.
The authors of this article sought to describe extracorporeal removal of linezolid and the main PK-PD parameter changes observed in critically ill septic patients with AKI, who are on CRRT.
Methods
The study authors systematically reviewed literature on PubMed up to January 2016. Studies of adult patients on linezolid and CRRT were considered eligible for the analysis only if operational settings of the CRRT machine, membrane type, linezolid blood concentrations and main PK-PD parameters were all clearly reported.
Results
Nine articles that included 49 patients were considered eligible for the analysis. The most common form of CRRT in the studies was continuous veno-venous hemofiltration (CVVH). The extracorporeal clearance values of linezolid across the different modalities were 1.2–2.3 L/h for CVVH, 0.9–2.2 L/h for hemodiafiltration and 2.3 L/h for hemodialysis, and large variability in PK/PD parameters was reported.
Conclusion
The authors concluded:
Wide variability in linezolid PK/PD parameters has been observed across critically ill septic patients with AKI treated with CRRT. Particular attention should be paid to linezolid therapy in order to avoid antibiotic failure in these patients. Strategies to improve the effectiveness of this antimicrobial therapy (such as routine use of target drug monitoring, increased posology or extended infusion) should be carefully evaluated, both in clinical and research settings.
Discussion
Unfortunately, therapeutic drug monitoring is not available at the bedside for most antibiotics, including linezolid. When using antibiotics in a patient on CRRT monitoring the response to treatment is particularly important. While this study does not provide definitive guidance on how to dose linezolid in patients on CRRT it does provide an important warning:
Just because an antibiotic is hepatically metabolized like linezolid doesn’t mean that it is not significantly affected by continuous renal replacement therapy.
Drug information question
Q: Should insulin detemir be given once or twice daily?
A: It depends on the dose.
At doses of 0.4 units/kg and higher, insulin detemir acts similar to other once daily insulins such as insulin glargine.
But at low doses around 0.2 units/kg such as what is often given to critically ill patients on tube feedings, insulin detemir acts more like NPH insulin.
Resource
The resource LiverTox is great for researching the hepatotoxicity potential of a given medication. Produced by the US National Library of Medicine, LiverTox provides up-to-date, accurate, and easily accessed information on the diagnosis, cause, frequency, patterns, and management of liver injury attributable to prescription and nonprescription medications, herbals and dietary supplements. LiverTox also includes a case registry that will enable scientific analysis and better characterization of the clinical patterns of liver injury. The LiverTox website provides a comprehensive resource for physicians and their patients, and for clinical academicians and researchers who specialize in idiosyncratic drug induced hepatotoxicity.
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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