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Cystatin C and/or creatinine-based estimated glomerular filtration rate for prediction of vancomycin clearance in long-stay critically ill patients with persistent inflammation, immunosuppression and catabolism syndrome (PICS): a population pharmacokinetics analysis
- Source :
- Internal and Emergency Medicine. 16:1883-1893
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Persistent inflammation, immunosuppression and catabolism syndrome (PICS) in critically ill patients are associated with unreliable creatinine (Cr)-based estimated glomerular filtration rate (eGFR) and alteration in vancomycin clearance (CL) due to ongoing muscle wasting and renal dysfunction (RD). Currently, cystatin C (Cys) is of great interest for eGFR due to its muscle independence. Patients receiving intravenous vancomycin with trough concentration monitoring after intensive care unit stay ≥ 14 days were retrospectively enrolled. Those with C-reactive protein > 30.0 mg/L, lymphocytes count 10% were diagnosed with PICS. Impact of PICS on vancomycin trough achievement was analyzed. Plasma Cys and Cr levels with their eGFRs in RD were compared in patients with and without PICS. Furthermore, the performance of eGFRs in predicting vancomycin CL was quantificationally evaluated by population pharmacokinetics (PPK) analysis using the Phoenix NLME software. Of 69 enrolled patients, 32 (46.4%) were PICS. PICS was predictive of Cr-guided vancomycin supratherapeutic trough concentrations (OR = 5.26, P = 0.013). Significant elevation of Cys, not of Cr, was observed in patients with PICS suffering from RD (P = 0.022), causing substantial differences among eGFRs. Fifty-two and 17 patients were enrolled for the modeling group and validation group, respectively. A one-compartment PPK model with first-order elimination adequately described the data of 126 Ctrough. Prediction of vancomycin CL with Cys and Cr-based eGFR (CKD-EPIcys-cr) significantly reduced the interindividual variability of CL (from 75.6 to 28.5%). External validation with 34 Ctrough showed the robustness and accuracy of this model. This study showed the negative impact of PICS on Cr-guided vancomycin trough achievement. PPK model with CKD-EPIcys-cr can be used to optimize vancomycin dosage in patients with PICS.
- Subjects :
- Male
medicine.medical_specialty
Critical Illness
medicine.medical_treatment
Renal function
030204 cardiovascular system & hematology
Gastroenterology
law.invention
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Vancomycin
law
Internal medicine
Internal Medicine
Humans
Medicine
Trough Concentration
030212 general & internal medicine
Cystatin C
Wasting
Aged
Retrospective Studies
Immunosuppression Therapy
Inflammation
Creatinine
biology
business.industry
Immunosuppression
Middle Aged
biochemical phenomena, metabolism, and nutrition
Intensive care unit
Anti-Bacterial Agents
chemistry
Emergency Medicine
biology.protein
Female
medicine.symptom
business
Glomerular Filtration Rate
medicine.drug
Subjects
Details
- ISSN :
- 19709366 and 18280447
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Internal and Emergency Medicine
- Accession number :
- edsair.doi.dedup.....c47725a9b46d571c7a10ca3e6060e695