In this episode I’ll:
1. Discuss an article about allometric dosing of vancomycin.
2. Answer the drug information question “How long should steroids be given for severe alcoholic hepatitis?”
3. Share a resource for calculating the allometric dosing of vancomycin.
Article
Allometric versus consensus guideline dosing in achieving target vancomycin trough concentrations
Lead author: Matthew L. Brown
Published in American Journal of Health-System Pharmacy May 2017
Background
Vancomycin is a challenging drug to dose correctly. You can drive a bus through the volume of distribution range (0.4 to 1 L/kg). You can have a patient therapeutic one day and toxic the next. Using vancomycin in obese patients is particularly difficult because weight-based dosing tends to result in over-dosing. The authors of this study compared consensus guidelines with a vancomycin dosing regimen based on allometry (the study of the relationship between body size and physiology) to determine vancomycin dose.
Methods
This study was a single-center, retrospective pre and post-implementation study of adults treated with IV vancomycin. The allometric formula to calculate the dose of vancomycin was 1,200 mg × [TBW (kg)/80 kg]^0.5.
Patients in the pre-implementation group received vancomycin 15-20 mg/kg IV calculated using total body weight. Patients in the post-implementation group received vancomycin based on the allometric dose.
The primary outcome was the attainment of an initial vancomycin trough concentration within the target range of 10–20 mg/L. A secondary outcome was the rate of nephrotoxicity associated with each dosing method.
For both groups the frequency of dosing was based on creatinine clearance cutoffs as follows:
>74 mL/min = q8h dosing
50-74 mL/min = q12h dosing
25-49 mL/min = q24h dosing
Results
The allometric dosing group achieved target trough concentration in 77% of the patients. The consensus guideline group achieved target trough concentration in 57% of the patients. This difference was statistically significant. When only obese patients were analyzed, the superiority of allometric dosing was maintained at 73% vs 46% in target range with allometric vs guideline dosing, respectively. While the rate of nephrotoxicity was not statistically different, there was a trend that favored the allometric group (1.2% vs 7.4%).
Conclusion
The authors concluded:
In hospitalized adults, allometric vancomycin dosing achieved a higher frequency of initial vancomycin trough concentrations within the target range of 10–20 mg/L, compared with dosing as recommended by consensus guidelines. The difference between methods in the percentage of troughs within the target range was most pronounced in obese patients.
Discussion
This is an exciting development for improving vancomycin dosing. A 77% rate of achieving target trough range is phenomenal. Allometric dosing results in using less vancomcyin on a mg/kg basis, and the potential for improved safety with allometric dosing should be explored.
The protocols for the study used some unique calculation methods that should be considered if attempting to replicate the results. The authors rounded doses to the nearest 100 mg whereas many institutions round to the nearest 250 mg. The authors also rounded low creatinine values in elderly patients up for the purposes of calculating creatinine clearance with a threshold of 1 mg/dL for patients 65 and older and 1.2 mg/dL for patients 80 and older.
The generalizability of these results to critically ill patients is low. No patient in the study received a loading dose of vancomycin. Only 30% of patients in the study were admitted to the ICU. The indication for vancomycin was skin and soft tissue infection more than half of the time. Only 2% of patients in the allometric group were receiving vancomycin for bacteremia.
Nevertheless this study provides an excellent set of questions for future research.
Many hospital-based vancomycin dosing protocols are empirically derived and locally monitored by medication use evaluation, Therefore, it is appropriate for individual hospitals to consider trialing and monitoring a vancomycin dosing regimen based on the results of this study.
Drug information question
Q: How long should steroids be given for severe alcoholic hepatitis?
A: 28 days before tapering slowly.
The 28-day duration is taken from a meta-analysis of five RCTs that showed that corticosteroids significantly improve 28-day survival in patients with severe alcoholic hepatitis.
A slow taper of 2-4 weeks helps ensure that adrenal insufficiency does not occur.
Keep in mind that prednisone needs to be converted by the liver to an active metabolite, so patients being treated for severe alcoholic hepatitis should receive prednisolone instead.
Resource
The resource for this episode is an allometric dosing calculator that I have created. The calculator replicates the formula used in the study discussed in this episode, including rounding to the nearest 100 mg. The calculator can be found here or by selecting the “calculator” page from the drop-down under “resources” in the menu for this site. A big shout out to “Pharmacy Matthew” – the lead author of the allometric vancomycin dosing study who helped me get the coding for the formula correctly implemented!
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.
Seems like a target trough of 10-20 should be pretty easy to hit !
We try to get a little tiighter on troughs majority 10-15 goals occasional 15-20 for MICs of 1