Corey Diamond, PharmD
Prolonged intermittent renal replacement therapy (PIRRT)—dialysis sessions given over 6 to 12 hours—is an increasingly used treatment strategy for critically ill patients with acute kidney injury. A compromise between intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT), PIRRT may have better hemodynamic tolerability compared to IHD and lower costs compared to CRRT.
Until now, there’s been an absence of clear guidance regarding antimicrobial dosing for patients undergoing PIRRT. A new systematic review, published online in Pharmacotherapy on August 19, 2023, now offers clinicians an evidence-based antimicrobial dosing guideline for critically ill patients on PIRRT.
Grewal and colleagues’ systematic review had three objectives: To identify and describe the pharmacokinetics of antimicrobials used in critically ill adults receiving PIRRT; to evaluate the quality of evidence supporting the collected data; and to propose dosing recommendations based on the synthesis of the collected data.
Thirty-nine studies enrolling 452 patients met criteria for inclusion and provided PK and/or PD data for 20 antimicrobials in critically ill adults receiving PIRRT. The quality of evidence was deemed strong for 7 out of 20 antimicrobials, and strong dosing recommendations were determined for 9 out of 20 antimicrobials studied.
Dosing recommendations
For each antimicrobial included in the report, the authors evaluated the body of evidence using a standardized framework. This included data from previous studies, how often and how long the PIRRT was given, the risk of adverse effects, and if computer simulations showed the right dose would be reached. The physiochemical properties of the antimicrobials were also considered.
If there were multiple pharmacodynamic targets used between studies for an antimicrobial, the most aggressive target was used in the dosing recommendation. Additionally, all dosing recommendations were intended for critically ill patients of an average weight of roughly 187 lbs (85 kg) receiving PIRRT daily for 8 hours.
Ultimately, the GRADE method was used to score the strength of the dosing recommendation for each antimicrobial.
The authors noted that despite an overall low quality of evidence, strong recommendations were able to be made for almost half of the identified antimicrobials. However, knowledge gaps persist for many antimicrobials, they continued, and higher quality studies (i.e., population PK studies with assessment of PD target attainment) are needed to address these gaps.
Finally, the authors state that the dosing recommendations are based on the likelihood of achieving a pharmacodynamic target, rather than a clinical outcome and the dosing recommendations may not be applicable if the local operational characteristics of PIRRT, minimum inhibitory concentrations of the organisms being targeted, or the pharmacodynamic targets differ from those used in original studies. ■
