Evaluation of Renal Function Estimation Formulas Specific to Dynamic Renal Function for Drug Dosing in Critically Ill Patients

The impact of ceftriaxone pharmacokinetic alterations on protein binding and PK/PD target attainment still remains unclear. We evaluated pharmacokinetic/pharmacodynamic (PK/PD) target attainment of unbound ceftriaxone in critically ill patients with severe community-acquired pneumonia (CAP). Besides, we evaluated the accuracy of predicted vs. measured unbound ceftriaxone concentrations, and its impact on PK/PD target attainment. A prospective observational cohort study was carried out in adult patients admitted to the intensive care unit with severe CAP. Ceftriaxone 2 g q24h intermittent infusion was administered to all patients. Successful PK/PD target attainment was defined as unbound trough concentrations above 1 or 4 mg/L throughout the whole dosing interval. Acceptable overall PK/PD target attainment was defined as successful target attainment in ≥90% of all dosing intervals. Measured unbound ceftriaxone concentrations (CEFu) were compared to unbound concentrations predicted from various protein binding models. Thirty-one patients were included. The 1 mg/L and 4 mg/L targets were reached in 26/32 (81%) and 15/32 (47%) trough samples, respectively. Increased renal function was associated with the failure to attain both PK/PD targets. Unbound ceftriaxone concentrations predicted by the protein binding model developed in the present study showed acceptable bias and precision and had no major impact on PK/PD target attainment. We showed suboptimal (i.e., <90%) unbound ceftriaxone PK/PD target attainment when using a standard 2 g q24h dosing regimen in critically ill patients with severe CAP. Renal function was the major driver for the failure to attain the predefined targets, in accordance with results found in general and septic ICU patients. Interestingly, CEFu was reliably predicted from CEFt without major impact on clinical decisions regarding PK/PD target attainment. This suggests that, when carefully selecting a protein binding model, CEFu does not need to be measured. As a result, the turn-around time and cost for ceftriaxone quantification can be substantially reduced.

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Neutrophil Gelatinase-Associated Lipocalin as a Marker for Renal Dysfunction Detection in Critically Ill Patients with Increased Intraabdominal Pressure

The Journal of Critical Care Medicine ◽

10.1515/jccm-2017-0006 ◽

2017 ◽

Vol 3 (1) ◽

pp. 24-28

Author(s):

Claudiu Puiac ◽

Janos Szederjesi ◽

Alexandra Lazăr ◽

Codruța Bad ◽

Lucian Pușcașiu

Keyword(s):

Renal Function ◽

Intensive Care ◽

Creatinine Clearance ◽

Critically Ill ◽

Critically Ill Patients ◽

Abdominal Cavity ◽

Intraabdominal Pressure ◽

Abdominal Pressure ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Neutrophil Gelatinase

Abstract Introduction: Elevated intraabdominal pressure (IAP) it is known to have an impact on renal function trough the pressure transmitted from the abdominal cavity to the vasculature responsible for the renal blood flow. Intraabdominal pressure is found to be frequent in intensive care patients and also to be a predictor of mortality. Intra-abdominal high pressure is an entity that can have serious impact on intensive care admitted patients, studies concluding that if this condition progresses to abdominal compartment syndrome mortality is as high as 80%. Aim: The aim of this study was to observe if a link between increased intraabdominal pressure and modification in renal function exists (NGAL, creatinine clearance). Material and Method: The study enrolled 30 critically ill patients admitted in the Intensive Care Unit of SCJU Tîrgu Mures between November 2015 and August 2016. The study enrolled adult, hemodynamically stable patients admitted in intensive critical care - defined by a normal blood pressure maintained without any vasopressor or inotropic support, invasive monitoring using PICCO device and abdominal pressure monitoring. Results: The patients were divided into two groups based on the intraabdominal pressure values: normal intraabdominal pressure group= 52 values and increased intraabdominal group= 35 values. We compared the groups in the light of NGAL values, 24 hours diuresis, GFR and creatinine clearance. The groups are significantly different when compared in the light of NGAL values and GFR values. We obtained a statistically significant correlation between NGAL value and 24 hour diuresis. No other significant correlations were encountered between the studied items. Conclusions: NGAL values are increased in patients with high intraabdominal pressure which may suggest its utility as a cut off marker for patients with increased intraabdominal pressure. There is a significant decreased GFR in patient with elevated intraabdominal pressure, observation which can help in early detection of renal injury in patients due to high intraabdominal pressure. No correlation was found between creatinine clearance and increased intraabdominal pressure.

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