How to Dose Medications During a PIRRT

Because HD, and subsequently CRRT, have been around for many years, dosing recommendations for medications are generally well established when using these modalities.

However, PIRRT dosing often leads to clinical pharmacists scratching their heads.

If there are no dosing recommendations listed in our ever-so-trusty drug information databases, how should meds be dosed for PIRRT?

A brief overview of CRRT vs PIRRT:

CRRT

• Encompasses continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), and continuous venovenous hemodiafiltration (CVVHDF), and slow continuous ultrafiltration (SCUF) 
  • Delivered for 24 hrs per day but is prone to frequent interruptions due to clotting of the filter
  • CVVH – Solute clearance through convection
  • CVVHD – Solute clearance through diffusion
  • CVVHDF – Solute clearance through convection and diffusion
  • SCUF – Removes fluid without the need for replacement solutions but has limited effects on the removal of waste products and electrolytes

PIRRT

• Encompasses sustained low-efficiency dialysis (SLED), sustained low-efficiency daily diafiltration (SLEDD-f), extended daily dialysis (EDD), and accelerated venovenous hemofiltration (AVVH)
  • Typically delivered for 6-12 hours per day
  • Utilizes HD machines with low blood-pump speeds and low dialysate flow rates
  • Allows for improved hemodynamic stability similar to CRRT

Dosing limitations and considerations:

Because drug manufacturers are not required to study how renal replacement therapies alter clearance, there is often a paucity of information. While there is definitely more information on HD and CRRT dosing, PIRRT dosing information is frequently lacking. 

The duration of PIRRT also varies between hospitals and published studies making a standardized approach to dosing an issue. Furthermore, the literature that is available is unfortunately limited to antimicrobials only. 

Until we have more data and based on the scant literature that is available if commonly used drug databases such as Lexicomp and Micromedex do not contain dosing recommendations for PIRRT, then the following pearls should be applied:

1. Antimicrobials for PIRRT should be dosed as they would be for CRRT
2. For antimicrobials are usually given every 24 hours that are significantly removed by dialysis, administration of the daily dose should be done after PIRRT each day
3. For antimicrobials are normally given every 12 hours that are significantly removed by dialysis, the dose should be given after PIRRT and then 12 hours later

De-brief:

• PIRRT is a hybrid of the renal replacement therapies HD and CRRT
• Dosing recommendations for PIRRT are lacking and the literature that is available is limited to antimicrobials
• When no published dosing recommendations are available, antimicrobials for PIRRT should be dosed similarly to CRRT
  • Antimicrobials dosed every 24 hours that are significantly removed by dialysis should be administered after completion of PIRRT each day
  • Antimicrobials normally dosed every 12 hours that are significantly removed by dialysis should be given after completion of PIRRT and then again 12 hours later

References:

1. Kitchlu A, Adhikari N, Burns K, et al. Outcomes of sustained low-efficiency dialysis versus continuous renal replacement therapy in critically ill adults with acute kidney injury: a cohort study. BMC Nephrol 2015;16:127.
2. Berbece A, Richardson R. Sustained low-efficiency dialysis in the ICU: Cost, anticoagulation, and solute removal. Kidney Int 2006;70:963-968.
3. Mushatt D, Mihm L, Dreisbach A, et al. Antibiotic dosing in slow extended daily dialysis. Clin Infect Dis 2009; 49:433-7.
4. Bogard K, Peterson N, Plumb T, et al. Antibiotic dosing during sustained low-efficiency dialysis: Special considerations in adult critically ill patients. Crit Care Med 2011; 39:3