Meropenem pharmacokinetics in critically ill patients with or without burn treated with or without continuous veno-venous haemofiltration.
Br J Clin Pharmacol
; 88(5): 2156-2168, 2022 05.
Article
in En
| MEDLINE
| ID: mdl-34773921
ABSTRACT
INTRODUCTION:
Severe burn injury involves widespread skin and tissue damage leading to systemic inflammation, hypermetabolism and multi-organ failure. The hypermetabolic phase of burn injury has been associated with increased systemic antibiotic clearance; however, critical illness in the absence of burn may also induce similar physiologic changes. Continuous renal replacement therapy (CRRT) is often implemented in critically ill patients and may also affect antibiotic clearance. Although the pharmacokinetics (PK) of meropenem has been described in both the burn and non-burn critically ill populations, direct comparative data is lacking.METHODS:
For this study, we evaluated PK parameters of meropenem from 23 critically ill patients, burn or non-burn, treated with or without continuous veno-venous haemofiltration (CVVH) to determine the contribution of burn and CVVH to the variability of therapeutic meropenem levels.RESULTS:
A two-compartment model best described the data and revealed creatinine clearance (CrCl) and total burn surface area (TBSA) as significant covariates on clearance (CL) and peripheral volume of distribution (Vp), respectively. Of interest, non-burn patients on CVVH displayed an overall lower inherent CL as compared to burn patients on CVVH (6.43 vs. 12.85 L/h). Probability of target attainment (PTA) simulations revealed augmented renal clearance (ARC) may necessitate dose adjustments, but TBSA and CVVH would not.CONCLUSIONS:
We recommend a standard dose of 1000 mg every 8 hours; however, if ARC is suspected, or the severity of illness requires a more stringent therapeutic target, we recommend a loading dose of 1000-2000 mg infused over 30 minutes to 1 hour followed by continuous infusion (3000-6000 mg over 24 hours), or intermittent infusion of 2000 mg every 8 hours.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Burns
/
Renal Insufficiency
/
Continuous Renal Replacement Therapy
Limits:
Humans
Language:
En
Journal:
Br J Clin Pharmacol
Year:
2022
Document type:
Article
Affiliation country:
United States