Prescribing in the critically ill patient can be a challenge due to a number of factors impacting on pharmacology:
- variable enteral absorption and interaction with enteral feed
- less protein binding in hypoalbuminaemic states
- extravascular volume expansion with fluid loading and capillary leak can alter the volume of distribution
- altered hepatic metabolism of drugs
- impaired renal excretion
- accumulation of toxic metabolites
- removal by renal replacement therapy
- interaction with other drugs
There’s another factor to bear in mind, though, which has been recently highlighted in the context of antibiotic prescription: that of Augmented Renal Clearance (ARC).
Some ICU patients have supraphysiologic renal function. Several studies have demonstrated significant numbers of ICU patients with higher than normal creatinine clearance. This is thought to be due to varying combinations of the following factors:
- Low systemic vascular resistance and increased cardiac output leading to increased renal blood flow
- Above factors enhanced by aggressive fluid and vasoactive therapy in pursuit of haemodynamic targets
- These lead to increase delivery of solute to the kidneys and increased clearance
This can have implications for prescribing: the serum creatinine will not identify these patients, but it is possible that ARC will result in less effective therapy for a given dose of a renally-excreted drug, for example beta-lactam antibiotics.
An editorial by critical care physician Dr Andrew Shorr highlights the inadequacy of basing prescribing recommendations on data from the ex-vivo interaction between drug and pathogen:
‘To believe that all patients will respond in the same fashion and with the same trajectory is to become handcuffed by the median response noted in clinical trials……….The central fallacy of the bug-drug approach is that it misses the key role of the host.’
Sub-therapeutic initial β-lactam concentrations in select critically ill patients: association between augmented renal clearance and low trough drug concentrations
Chest. 2011 Dec 22. [Epub ahead of print] Free Full Text
Antibiotics in the critically ill: the bug, drug, host triad
Chest. 2012 Jul 1;142(1):8-10 Free Full Text