Clinical applicability of urinary creatinine clearance for determining the initial dose of vancomycin in critically ill patients

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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Influence of Mechanical Ventilation on the Pharmacokinetics of Vancomycin Administered by Continuous Infusion in Critically Ill Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01249-17 ◽

2017 ◽

Vol 61 (12) ◽

Cited By ~ 9

Author(s):

Susanna Edith Medellín-Garibay ◽

Silvia Romano-Moreno ◽

Pilar Tejedor-Prado ◽

Noelia Rubio-Álvaro ◽

Aida Rueda-Naharro ◽

...

Keyword(s):

Mechanical Ventilation ◽

Creatinine Clearance ◽

Continuous Infusion ◽

Critically Ill ◽

Critically Ill Patients ◽

Population Pharmacokinetic Model ◽

Pharmacokinetic Model ◽

Volume Of Distribution ◽

Stochastic Simulations ◽

Population Pharmacokinetic

ABSTRACT Pathophysiological changes involved in drug disposition in critically ill patients should be considered in order to optimize the dosing of vancomycin administered by continuous infusion, and certain strategies must be applied to reach therapeutic targets on the first day of treatment. The aim of this study was to develop a population pharmacokinetic model of vancomycin to determine clinical covariates, including mechanical ventilation, that influence the wide variability of this antimicrobial. Plasma vancomycin concentrations from 54 critically ill patients were analyzed simultaneously by a population pharmacokinetic approach. A nomogram for dosing recommendations was developed and was internally evaluated through stochastic simulations. The plasma vancomycin concentration-versus-time data were best described by a one-compartment open model with exponential interindividual variability associated with vancomycin clearance and the volume of distribution. Residual error followed a homoscedastic trend. Creatinine clearance and body weight significantly dropped the objective function value, showing their influence on vancomycin clearance and the volume of distribution, respectively. Characterization based on the presence of mechanical ventilation demonstrated a 20% decrease in vancomycin clearance. External validation (n = 18) was performed to evaluate the predictive ability of the model; median bias and precision values were 0.7 mg/liter (95% confidence interval [CI], −0.4, 1.7) and 5.9 mg/liter (95% CI, 5.4, 6.4), respectively. A population pharmacokinetic model was developed for the administration of vancomycin by continuous infusion to critically ill patients, demonstrating the influence of creatinine clearance and mechanical ventilation on vancomycin clearance, as well as the implications for targeting dosing rates to reach the therapeutic range (20 to 30 mg/liter).

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CP-184 Correlations of vancomycin clearance during intermittent infusion with measured and estimated creatinine clearance in critically ill patients: 6 hour urine collection may be beneficial

10.1136/ejhpharm-2017-000640.182 ◽

2017 ◽

Author(s):

B Shahrami ◽

F Najmeddin ◽

S Mousavi ◽

A Ahmadi ◽

MR Rouini ◽

...

Keyword(s):

Creatinine Clearance ◽

Critically Ill ◽

Critically Ill Patients ◽

Intermittent Infusion ◽

Urine Collection

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TWO HOUR VERSUS TWENTY-TWO HOUR CREATININE CLEARANCE IN CRITICALLY ILL PATIENTS

Critical Care Medicine ◽

10.1097/00003246-198604000-00190 ◽

1986 ◽

Vol 14 (4) ◽

pp. 407

Author(s):

Robert N. Sladen ◽

Eric Endo ◽

Thomas Harrison

Keyword(s):

Creatinine Clearance ◽

Critically Ill ◽

Critically Ill Patients

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The kinetic glomerular filtration rate is not interchangeable with measured creatinine clearance for prediction of piperacillin underexposure in critically ill patients with augmented renal clearance

Critical Care ◽

10.1186/s13054-018-2117-7 ◽

2018 ◽

Vol 22 (1) ◽

Cited By ~ 6

Author(s):

Cédric Carrié ◽

Sébastien Rubin ◽

Pierre Sioniac ◽

Dominique Breilh ◽

Matthieu Biais

Keyword(s):

Glomerular Filtration Rate ◽

Creatinine Clearance ◽

Glomerular Filtration ◽

Renal Clearance ◽

Critically Ill ◽

Critically Ill Patients ◽

Filtration Rate ◽

Augmented Renal Clearance

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Select Critically ill Patients at Risk of Augmented Renal Clearance: Experience in a Malaysian Intensive Care Unit

Anaesthesia and Intensive Care ◽

10.1177/0310057x1404200606 ◽

2014 ◽

Vol 42 (6) ◽

pp. 715-722 ◽

Cited By ~ 15

Author(s):

S. Adnan ◽

S. Ratnam ◽

S. Kumar ◽

D. Paterson ◽

J. Lipman ◽

...

Keyword(s):

Intensive Care Unit ◽

At Risk ◽

Intensive Care ◽

Serum Creatinine ◽

Creatinine Clearance ◽

Renal Clearance ◽

Critically Ill ◽

Critically Ill Patients ◽

Augmented Renal Clearance ◽

Drug Concentrations

Augmented renal clearance (ARC) refers to increased solute elimination by the kidneys. ARC has considerable implications for altered drug concentrations. The aims of this study were to describe the prevalence of ARC in a select cohort of patients admitted to a Malaysian intensive care unit (ICU) and to compare measured and calculated creatinine clearances in this group. Patients with an expected ICU stay of >24 hours plus an admission serum creatinine concentration <120 μmol/l, were enrolled from May to July 2013. Twenty-four hour urinary collections and serum creatinine concentrations were used to measure creatinine clearance. A total of 49 patients were included, with a median age of 34 years. Most study participants were male and admitted after trauma. Thirty-nine percent were found to have ARC. These patients were more commonly admitted in emergency ( P=0.03), although no other covariants were identified as predicting ARC, likely due to the inclusion criteria and the study being under-powered. Significant imprecision was demonstrated when comparing calculated Cockcroft-Gault creatinine clearance (Crcl) and measured Crcl. Bias was larger in ARC patients, with Cockcroft-Gault Crcl being significantly lower than measured Crcl ( P <0.01) and demonstrating poor correlation (rs=-0.04). In conclusion, critically ill patients with ‘normal’ serum creatinine concentrations have varied Crcl. Many are at risk of ARC, which may necessitate individualised drug dosing. Furthermore, significant bias and imprecision between calculated and measured Crcl exists, suggesting clinicians should carefully consider which method they employ in assessing renal function.

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Dalteparin Thromboprophylaxis in Critically Ill Patients with Severe Renal Insufficiency: The Direct Study.

Blood ◽

10.1182/blood.v110.11.304.304 ◽

2007 ◽

Vol 110 (11) ◽

pp. 304-304

Author(s):

James Douketis ◽

Deborah Cook ◽

Nicole Zytaruks ◽

Diane Heels-Ansdell ◽

Mark Crowther

Keyword(s):

Renal Insufficiency ◽

Creatinine Clearance ◽

Critically Ill ◽

Critically Ill Patients ◽

Bleeding Risk ◽

Open Label ◽

Once Daily ◽

Major Bleed ◽

Severe Renal Insufficiency ◽

Pharmacodynamic Profile

Abstract Background: Critically ill patients with renal insufficiency are at high risk for deep vein thrombosis (DVT). Low-molecular-weight heparins (LMWHs) effectively prevent DVT but are avoided in patients with renal insufficiency because of potential bioaccumulation and potential bleeding risk. However, evidence is lacking that LMWHs bioaccumulate in such patients. Objectives: The objectives of DIRECT were, in critically ill patients with severe renal insufficiency, to determine if dalteparin prophylaxis leads to bioaccumulation and bleeding from excessive anticoagulation and to determine the pharmacodynamic profile of dalteparin. Methods: Multi-center, open-label, prospective cohort study of critically ill patients with a creatinine clearance <30 mL/min who receive dalteparin, 5000 IU once-daily, subcutaneously for up to 30 days. Dalteparin bioaccumulation in a patient was defined by a trough anti-Xa level >0.40 IU/mL, measured twice-weekly 20 hours after the prior dalteparin dose. The pharmacodynamic profile of dalteparin was assessed by anti-Xa levels measured at 0, 1, 2, 4, 8, 12, 20, and 24 hours after the prior dose on days 3, 10, and 17 of treatment. Results: We enrolled 156 patients with a mean (SD) creatinine clearance of 18.9 (6.5) mL/min; of these, 18 were excluded because they died or were discharged before testing (n = 3) or had prevalent DVT (n = 14) or pulmonary embolism (n = 1) within 48 hours of enrollment. Of 138 patients included, the median (inter-quartile range [IQR]) duration of dalteparin treatment was 7 days (4, 12). In 120 pa tients who had ≥1 trough anti-Xa measured (427 total), none had dalteparin bioaccumulation; the median (IQR) trough anti-Xa level was <0.1 IU/mL (<0.1, <0.1). In 138 patients who received ≥1 dose of dalteparin,10 patients (7.2%; 95% CI: 4.0, 12.8) had a major bleed, all with trough anti-Xa levels ≤0.18 IU/mL. The pharmacodynamic profile of dalteparin, shown in the Figure, was typical for drugs that do not bioaccumulate, with a typical peak and decline after 3, 10, and 17 days of treatment. Conclusions: In critically ill patients with severe renal insufficiency, thromboprophylaxis with dalteparin did not bioaccumulate. Dalteparin, 5000 IU once-daily, appears to be a reasonable option for thromboprophylaxis of critically ill patients with severe renal insufficiency. Figure Figure

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High creatinine clearance in critically ill patients with community-acquired acute infectious meningitis

BMC Nephrology ◽

10.1186/1471-2369-13-124 ◽

2012 ◽

Vol 13 (1) ◽

Cited By ~ 15

Author(s):

Alexandre Lautrette ◽

Thuy-Nga Phan ◽

Lemlih Ouchchane ◽

Ali AitHssain ◽

Vincent Tixier ◽

...

Keyword(s):

Creatinine Clearance ◽

Critically Ill ◽

Critically Ill Patients

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Estimating creatinine clearance for Malaysian critically ill patients with unstable kidney function and impact on dosage adjustment

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i3.2358 ◽

2020 ◽

Vol 11 (3) ◽

pp. 2825-2837

Author(s):

Yen Ping Ng ◽

Angel Wei Ling Goh ◽

Chee Ping Chong

Keyword(s):

Creatinine Clearance ◽

Critically Ill ◽

Kidney Function ◽

Critically Ill Patients ◽

Dosage Adjustment ◽

Drug Regimen ◽

Significant Difference ◽

Clinically Significant ◽

Kidney Functions ◽

The Impact

It is an essential requirement to estimate glomerular filtration rate in dosing adjustment of drug treatment for critically ill patients with unstable kidney function. Previous studies showed that Cockcroft-Gault equation was not appropriate for the assessment of unstable kidney function. However, there is a lack of assessment on other equations specifically designed for fluctuating kidney functions. This study is aimed to evaluate the differences between estimated creatinine clearances by using Cockcroft-Gault, Jelliffe, Brater, and Chiou equations and the impact on dosing adjustment of renally excreted drugs for critically ill patients with unstable kidney function. A retrospective observational study was conducted among 103 patients with unstable kidney function who were admitted to intensive care unit of Taiping Hospital, Malaysia. Serum creatinine levels from day 1 to 7 of admission were collected. The median differences of estimated creatinine clearance based on the four different equations were analysed by Friedman-ANOVA test. The median estimated creatinine clearances when patients were having fluctuating kidney functions showed 35.69 ml/min (IQR: 22.57 – 53.97) by Cockcroft-Gault and 22.64 ml/min (IQR: 10.46 – 38.49) by Jelliffe equation, while Brater and Chiou equations showed 35.88 ml/min (IQR: 19.46 – 56.04) and 30.10 ml/min (IQR: 16.55 – 46.82) respectively. Jelliffe and Chiou equation showed a significant 36.56% and 15.66% lower estimated creatinine clearance respectively as compared to Cockcroft-Gault (p < 0.001). Meanwhile, there was no significant difference between Brater and Cockcroft-Gault equation. Jelliffe equation demonstrated the lowest estimated creatinine clearance value with a more intense dosage adjustment required for patients’ drug regimen involving renally excreted drugs. In conclusion, there were clinically significant variations in the estimated creatinine clearance from the different equations.

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