ABSTRACTS from 16th International COnference on ... - CRRT Online

Therapeutic Drug Monitoring During Dialysis Support
Educational Objectives:
1. Understanding how pharmacokinetics of antibiotics differ in the critically ill
2. Understand the different clearances of antibiotics in CRRT
Jeffrey Lipman MD
4:15-4:30
Thursday, February 16
3. Understand what therapeutic drug monitoring means and its value in such circumstances
Content Description:
Maximising effectiveness (not underdosing) whilst minimising toxicity (not overdosing) of antimicrobial agents
should be the goal for treating infections.
Before being released onto the open market antimicrobial dosing is tested in non-ICU patients (Phase 2 and 3
drug trials). These patients have relatively normal cardiovascular systems with normal organ blood flow. The
ICU patients that need antimicrobials often have significant systemic inflammation (leaky capillaries), need significant
fluid resuscitation, with or without inotropic support. It is not surprising then that the critically ill patient
has altered pharmacokinetics. Yet we often give the same dose to these patients as the “package insert” The volume
of distribution of antimicrobials is increased, hence necessitating large loading doses. Hypoaluminemia
often complicates protein binding thereby making dosing even more difficult. Organ dysfunction will decrease
clearances yet dialysis removes some drugs.
The systems and technology for Intermittent HemoDialysis (IHD) across the world have been relatively well
defined, as have the prescriptions for the patient with chronic renal failure (CRF). Drug dosing during IHD has a
relatively well validated set of rules. The various modalities in which CRRT have been used (CVVH vs CVVHD
vs CVVHDF vs SLED) makes a “one size fits all” cookbook recipe impossible to prescribe due to differing
blood flow, filter characteristics, effluent rates and time on filter.
Drug levels (hence indirectly therapeutic drug monitoring) are often available for aminoglycosides and vancomicin
largely due to toxicity. The safety of beta-lactams is wide and hence there has been little such drug monitoring.
TDM can be used to personalize dosing without allowing toxicity, yet preventing resistance and treatment
failure. With easier technology available for the measurement of the beta-lactams, TDM will become more
common.
With the altered PK of antimicrobials in the ICU and particularly with the difficult to measure clearances of such
in CRRT, TDM will allow better optimisation of antibiotic administration. We have shown significant underdosing
and overdosing of such drugs in the ICU.
TDM serves as an accurate method of dose adjustment of antimicrobial agents in difficult to predict circumstances
Suggested Reading:
1. Roberts JA, Lipman J. Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med
2009;37:840-851
2. Lipman J, Udy AA, Roberts JA. Do we understand the impact of altered physiology, consequent interventions,
and resultant clinical scenarios in ICU? The antibiotic story. Anaesth Intens Care 2011;39: 999-1000.
3. Roberts JA, Taccone FS, Udy AA, Vincent JL, Jacobs F, Lipman J. Vancomycin dosing in critically ill patients –
robust methods for improved continuous infusion regimens. Antimicrob Agents Chemother 2011;55:2704-2709.
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