ADS – Clinical pharmacokinetics approach to aminoglycoside and vancomycin dosing

I found myself repeating the old adage from 2nd year pharmacokinetics that Dr. Ensom said: “if you want the chicken to be finger lickin’ good, you have to use the Colonel’s recipe!” For the majority of patients, the “recipe”, i.e. dosing protocol will work just fine, but this session was mostly me trying to remember how the heck I even knew how to use those equations in The Kentucky Manual…anyway, here are some pertinent points I got from the morning’s session.

Aminoglycosides (Vd = 0.2-0.3 L/kg and t1/2 = 2 hours for adults);  – use the VCH dosing protocol for traditional or extended interval dosing. Do NOT use extended interval in: pregnancy, burns >20% BSA, pts on dialysis, or septic shock. Basically anyone who would have increased clearance such that the post-antibiotic effect will not extend to 24 hours.
To load or not to load? – YES, unless you are doing once-daily extended interval dosing.
When do you take a level? – before the 3rd dose within 30 mins, and 30 mins after the half-hour infusion (4th dose). No levels for extended interval dosing as the trough will be undetectable anyway.
How do you monitor for toxicities? – vestibular toxicity manifests in 1-2 weeks, so get audiology involved if you suspect it. Nephrotoxicity happens quicker.
Adjusting doses based on levels – if your patient’s renal function is stable, and their clinical course is stable, and they have received all their doses and are at steady state… you can use the “cheat” method for a peak level. For everything else, there’s Masterca- The Kentucky Manual. Also useful if the levels were not drawn correctly at the right time.

The “cheat” equation: New dose = old dose * (desired level/actual level) 

Vancomycin (Vd = 0.6-0.8 L/kg and t1/2 = 4-6 hours for adults) – use the VCH/PHC dosing protocol.
To load or not to load? – YES…although in the course of doing the literature search for my project, I found that the evidence of a loading dose is not very extensive, but if a patient’s bacteremic, or they have meningitis, you wouldn’t deny them a load, right?
When do you take a level? – I thought this was cut and dry, before the 4th dose then use the cheat equation above to adjust the dose. HOWEVER, Dr. Loh presented an interesting case where one would have to improvise. A level may not even be warranted for an otherwise healthy patient who may not get vanco past 7 days. Post-levels are usually not indicated, and only reserved for unique cases such as in the case of renal failure or burns, or unstable clinical status warranting calculation of individual PK parameters.
In the setting of fulminant renal failure, it might be advisable to give a “mini-load” for the patient if a suboptimal dose was given in Emerg. After that, a random vanco level may be the best option just to see how the patient is clearing the drug.
If a load was given in Emerg, technically you could take a level pre-3rd dose assuming that the patient’s clinical status has remained stable. – the half-life of vanco is 4-6 hours, so steady state should be reached in 20-30 hours… assuming q12h dosing, that would fall within before the 3rd dose.
How do you monitor for toxicities? – there are some that are dose-related, i.e. red man syndrome and ototoxicity, and some that are not, such as nephrotoxicity (but really…vanco is not that nephrotoxic, one would be more worried about the other medications on board that may be nephrotoxic). NEUTROPENIA actually occurs in 1-10% of patients (as per Lexicomp) but it only manifests after 1-2 weeks of treatment.

Overall, I feel more confident than when I walked in that morning in terms of my ability to evaluate a patient’s AMG or vancomycin regimen. I also learned that sometimes you may have to improvise and think clinically to solve dosing issues – but that’s why we are on the ward! If everything were perfectly protocolized, physicians wouldn’t need us!

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