Estimating Aminoglycoside and Creatinine Clearance in Underweight Patients
Estimating Aminoglycoside and Creatinine Clearance in Underweight Patients
Purpose. An adjustment factor (AF) was developed and evaluated to determine the best method for estimating aminoglycoside clearance (CLamino) and creatinine clearance (CLcr) in underweight patients.
Methods. This study was a retrospective, multicenter, chart analysis of aminoglycoside pharmacokinetic data obtained between January 2000 and August 2006 at the University of Southern California University Hospital and Cedars-Sinai Medical Center. Adult patients were included in this study if they had received inpatient aminoglycoside therapy, were at least 60 inches tall, and were at least 10% below their ideal body weight (IBW). CLcr and CLamino were estimated and compared to actual CLamino using the Cockcroft–Gault equation with actual serum creatinine (SCr) (CGSCr), Cockcroft–Gault equation with SCr rounded to 1 mg/dL (CGrnd), and Cockcroft–Gault equation multiplied by an AF (CGAF).
Results. An AF of 0.69 was determined from 52 patients and tested in 53 separate patients. The CGAF method was more precise and less biased than the CGSCr equation; the CGrnd equation was less biased than the CGSCr equation; the CGAF method was more precise and less biased than the CGrnd equation, but this difference was not statistically significant. In underweight patients with an SCr concentration of ≥ 1 mg/dL, the CGAF method had less bias compared with the CGSCr equation.
Conclusion. Both the CGrnd and CGAF methods of predicting CLamino in underweight patients were superior to the CGSCr equation. The CGAF method was more accurate in patients exhibiting greater differences between IBW and actual body weight.
Estimation of creatinine clearance (CLcr) is a common method used for dosing and monitoring drugs excreted by the kidneys, such as the aminoglycoside antibiotics. Serum creatinine concentration (SCr) is among the most reliable markers of renal function, as creatinine is produced at a constant rate, almost exclusively cleared through glomerular filtration, and rapidly and inexpensively measured.
A 24-hour urine collection provides the most accurate CLcr when properly performed; however, this method is labor-intensive and time-consuming, making it impractical for use in immediate medication dosing. Consequently, several nomograms and equations have been developed to estimate CLcr from SCr, most of which account for age, weight, sex, and SCr. Of these methods, the equation developed by Cockcroft and Gault is one of the most universally used. However, these nomograms and equations may not sufficiently account for the fact that creatinine production diminishes with decreased muscle mass relative to body weight, such as in patients with muscular dystrophies, and when actual body weight (ABW) is significantly less than ideal body weight (IBW). In particular, patients with decreased muscle mass relative to body weight and with normal renal function often have a SCr below the normal range of 0.6–1.3 mg/dL. In these individuals, a lower SCr value is a reflection of reduced creatinine production rather than a higher rate of renal elimination. Consequently, the Cockcroft–Gault equation can overestimate CLcr in underweight patients, leading to a potential overdose of renally eliminated drugs.
Thus, estimation of CLcr from measured SCr using standard approaches in these situations is not advisable. In these instances, clinicians must decide how to factor the SCr into their estimate of CLcr. One common convention is to arbitrarily round a patient's SCr to 1 mg/dL, if it is less than that value. However, this practice is currently unsupported by clinical data. The value of 1 mg/dL is arbitrary, and this practice does not provide for adjustments when an underweight patient has an SCr concentration of ≥1 mg/dL due to reduced renal function, even though creatinine production is still diminished. Notwithstanding, the use of a "normalized" SCr value of 1 mg/dL has been shown to underestimate CLcr. Rounding the SCr concentration from 0.5 to 1.0 mg/dL reduces the estimate of CLcr by 50%, whereas rounding it from 0.8 mg/dL reduces the estimate by only 20%. Further, if an underweight patient with an SCr concentration of 0.5 mg/dL has renal impairment and the SCr rises to a new steady-state concentration of ≥1.0 mg/dL, the rounding method has no established utility to deal with this. In fact, the rounding method would yield the same estimated CLcr in the same patient when the SCr is 0.5–1.0 mg/dL, which is not logical. The lack of a clinically proven method for estimating CLcr in under-weight patients makes it difficult to dose renally eliminated drugs, such as the aminoglycosides, and may increase the risk of adverse events.
The objectives of this study were to develop and test an adjustment factor (AF) for estimating aminoglycoside clearance (CLamino) from the Cockcroft–Gault equation in underweight patients and to determine if this AF was related to the percent deviation from IBW by using measured SCr and SCr rounded to 1 mg/dL in the Cockcroft–Gault equation.
Abstract and Introduction
Abstract
Purpose. An adjustment factor (AF) was developed and evaluated to determine the best method for estimating aminoglycoside clearance (CLamino) and creatinine clearance (CLcr) in underweight patients.
Methods. This study was a retrospective, multicenter, chart analysis of aminoglycoside pharmacokinetic data obtained between January 2000 and August 2006 at the University of Southern California University Hospital and Cedars-Sinai Medical Center. Adult patients were included in this study if they had received inpatient aminoglycoside therapy, were at least 60 inches tall, and were at least 10% below their ideal body weight (IBW). CLcr and CLamino were estimated and compared to actual CLamino using the Cockcroft–Gault equation with actual serum creatinine (SCr) (CGSCr), Cockcroft–Gault equation with SCr rounded to 1 mg/dL (CGrnd), and Cockcroft–Gault equation multiplied by an AF (CGAF).
Results. An AF of 0.69 was determined from 52 patients and tested in 53 separate patients. The CGAF method was more precise and less biased than the CGSCr equation; the CGrnd equation was less biased than the CGSCr equation; the CGAF method was more precise and less biased than the CGrnd equation, but this difference was not statistically significant. In underweight patients with an SCr concentration of ≥ 1 mg/dL, the CGAF method had less bias compared with the CGSCr equation.
Conclusion. Both the CGrnd and CGAF methods of predicting CLamino in underweight patients were superior to the CGSCr equation. The CGAF method was more accurate in patients exhibiting greater differences between IBW and actual body weight.
Introduction
Estimation of creatinine clearance (CLcr) is a common method used for dosing and monitoring drugs excreted by the kidneys, such as the aminoglycoside antibiotics. Serum creatinine concentration (SCr) is among the most reliable markers of renal function, as creatinine is produced at a constant rate, almost exclusively cleared through glomerular filtration, and rapidly and inexpensively measured.
A 24-hour urine collection provides the most accurate CLcr when properly performed; however, this method is labor-intensive and time-consuming, making it impractical for use in immediate medication dosing. Consequently, several nomograms and equations have been developed to estimate CLcr from SCr, most of which account for age, weight, sex, and SCr. Of these methods, the equation developed by Cockcroft and Gault is one of the most universally used. However, these nomograms and equations may not sufficiently account for the fact that creatinine production diminishes with decreased muscle mass relative to body weight, such as in patients with muscular dystrophies, and when actual body weight (ABW) is significantly less than ideal body weight (IBW). In particular, patients with decreased muscle mass relative to body weight and with normal renal function often have a SCr below the normal range of 0.6–1.3 mg/dL. In these individuals, a lower SCr value is a reflection of reduced creatinine production rather than a higher rate of renal elimination. Consequently, the Cockcroft–Gault equation can overestimate CLcr in underweight patients, leading to a potential overdose of renally eliminated drugs.
Thus, estimation of CLcr from measured SCr using standard approaches in these situations is not advisable. In these instances, clinicians must decide how to factor the SCr into their estimate of CLcr. One common convention is to arbitrarily round a patient's SCr to 1 mg/dL, if it is less than that value. However, this practice is currently unsupported by clinical data. The value of 1 mg/dL is arbitrary, and this practice does not provide for adjustments when an underweight patient has an SCr concentration of ≥1 mg/dL due to reduced renal function, even though creatinine production is still diminished. Notwithstanding, the use of a "normalized" SCr value of 1 mg/dL has been shown to underestimate CLcr. Rounding the SCr concentration from 0.5 to 1.0 mg/dL reduces the estimate of CLcr by 50%, whereas rounding it from 0.8 mg/dL reduces the estimate by only 20%. Further, if an underweight patient with an SCr concentration of 0.5 mg/dL has renal impairment and the SCr rises to a new steady-state concentration of ≥1.0 mg/dL, the rounding method has no established utility to deal with this. In fact, the rounding method would yield the same estimated CLcr in the same patient when the SCr is 0.5–1.0 mg/dL, which is not logical. The lack of a clinically proven method for estimating CLcr in under-weight patients makes it difficult to dose renally eliminated drugs, such as the aminoglycosides, and may increase the risk of adverse events.
The objectives of this study were to develop and test an adjustment factor (AF) for estimating aminoglycoside clearance (CLamino) from the Cockcroft–Gault equation in underweight patients and to determine if this AF was related to the percent deviation from IBW by using measured SCr and SCr rounded to 1 mg/dL in the Cockcroft–Gault equation.
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