Augmented Renal Clearance Using Population-Based Pharmacokinetic Modeling in Critically Ill Pediatric Patients∗

Sean N. Avedissian, Erin Bradley, Diana Zhang, John S. Bradley, Lama H. Nazer, Tri M. Tran, Austin Nguyen, Jennifer Le

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Objectives: The objectives of this study were to: 1) evaluate the prevalence of augmented renal clearance in critically ill pediatric patients using vancomycin clearance; 2) derive the pharmacokinetic model that best describes vancomycin clearance in critically ill pediatric patients; and 3) correlate vancomycin clearance with creatinine clearance estimated by modified Schwartz or Cockcroft-Gault. Design: Retrospective, two-center, cohort study from 2003 to 2016. Setting: Clinical drug monitoring services in the PICUs at two tertiary care, teaching hospitals. Patients: Children from 1 to 21 years old. Interventions: None. Measurements and Main Results: Identify patients with augmented renal clearance (vancomycin clearance ≥ 130 mL/min/1.73 m2 used as definition of augmented renal clearance). Derive final population-based pharmacokinetic model and estimate individual patient pharmacokinetic parameters. Compare estimated glomerular filtration rate (modified Schwartz or Cockcroft-Gault depending on age < or ≥ 17 yr) with vancomycin clearance. Augmented renal clearance was identified in 12% of 250 total subjects. The final population-based pharmacokinetic model for vancomycin clearance (L/hr) was 0.118 × weight (e-1.13 × [serum creatinine (Scr)-0.40]). Median vancomycin clearance in those with versus without augmented renal clearance were 141.3 and 91.7 mL/min/1.73 m2, respectively (p < 0.001). By classification and regression tree analysis, patients who were more than 7.9 years old were significantly more likely to experience augmented renal clearance (17% vs 4.6% in those ≤ 7.9 yr old; p = 0.002). In patients with augmented renal clearance, 79% of 29 had vancomycin trough concentrations less than 10 μg/mL, compared with 52% of 221 in those without augmented renal clearance (p < 0.001). Vancomycin clearance was weakly correlated to the glomerular filtration rate estimated by the modified Schwartz or Cockcroft-Gault method (Spearman R2 = 0.083). Conclusions: Augmented renal clearance was identified in one of 10 critically ill pediatric patients using vancomycin clearance, with an increase of approximately 50 mL/min/1.73 m2 in those with augmented renal clearance. As augmented renal clearance results in subtherapeutic antibiotic concentrations, optimal dosing is essential in those exhibiting augmented renal clearance.

Original languageEnglish (US)
Pages (from-to)e388-e394
JournalPediatric Critical Care Medicine
Volume18
Issue number9
DOIs
StatePublished - Sep 1 2017

Fingerprint

Critical Illness
Vancomycin
Pharmacokinetics
Pediatrics
Kidney
Population
Glomerular Filtration Rate
Creatinine
Drug Monitoring
Tertiary Healthcare
Teaching Hospitals
Cohort Studies
Regression Analysis
Anti-Bacterial Agents
Weights and Measures

Keywords

  • antibiotics
  • clearance
  • critical care
  • pediatrics
  • pharmacokinetics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Critical Care and Intensive Care Medicine

Cite this

Augmented Renal Clearance Using Population-Based Pharmacokinetic Modeling in Critically Ill Pediatric Patients∗. / Avedissian, Sean N.; Bradley, Erin; Zhang, Diana; Bradley, John S.; Nazer, Lama H.; Tran, Tri M.; Nguyen, Austin; Le, Jennifer.

In: Pediatric Critical Care Medicine, Vol. 18, No. 9, 01.09.2017, p. e388-e394.

Research output: Contribution to journalArticle

Avedissian, Sean N. ; Bradley, Erin ; Zhang, Diana ; Bradley, John S. ; Nazer, Lama H. ; Tran, Tri M. ; Nguyen, Austin ; Le, Jennifer. / Augmented Renal Clearance Using Population-Based Pharmacokinetic Modeling in Critically Ill Pediatric Patients∗. In: Pediatric Critical Care Medicine. 2017 ; Vol. 18, No. 9. pp. e388-e394.
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abstract = "Objectives: The objectives of this study were to: 1) evaluate the prevalence of augmented renal clearance in critically ill pediatric patients using vancomycin clearance; 2) derive the pharmacokinetic model that best describes vancomycin clearance in critically ill pediatric patients; and 3) correlate vancomycin clearance with creatinine clearance estimated by modified Schwartz or Cockcroft-Gault. Design: Retrospective, two-center, cohort study from 2003 to 2016. Setting: Clinical drug monitoring services in the PICUs at two tertiary care, teaching hospitals. Patients: Children from 1 to 21 years old. Interventions: None. Measurements and Main Results: Identify patients with augmented renal clearance (vancomycin clearance ≥ 130 mL/min/1.73 m2 used as definition of augmented renal clearance). Derive final population-based pharmacokinetic model and estimate individual patient pharmacokinetic parameters. Compare estimated glomerular filtration rate (modified Schwartz or Cockcroft-Gault depending on age < or ≥ 17 yr) with vancomycin clearance. Augmented renal clearance was identified in 12{\%} of 250 total subjects. The final population-based pharmacokinetic model for vancomycin clearance (L/hr) was 0.118 × weight (e-1.13 × [serum creatinine (Scr)-0.40]). Median vancomycin clearance in those with versus without augmented renal clearance were 141.3 and 91.7 mL/min/1.73 m2, respectively (p < 0.001). By classification and regression tree analysis, patients who were more than 7.9 years old were significantly more likely to experience augmented renal clearance (17{\%} vs 4.6{\%} in those ≤ 7.9 yr old; p = 0.002). In patients with augmented renal clearance, 79{\%} of 29 had vancomycin trough concentrations less than 10 μg/mL, compared with 52{\%} of 221 in those without augmented renal clearance (p < 0.001). Vancomycin clearance was weakly correlated to the glomerular filtration rate estimated by the modified Schwartz or Cockcroft-Gault method (Spearman R2 = 0.083). Conclusions: Augmented renal clearance was identified in one of 10 critically ill pediatric patients using vancomycin clearance, with an increase of approximately 50 mL/min/1.73 m2 in those with augmented renal clearance. As augmented renal clearance results in subtherapeutic antibiotic concentrations, optimal dosing is essential in those exhibiting augmented renal clearance.",
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T1 - Augmented Renal Clearance Using Population-Based Pharmacokinetic Modeling in Critically Ill Pediatric Patients∗

AU - Avedissian, Sean N.

AU - Bradley, Erin

AU - Zhang, Diana

AU - Bradley, John S.

AU - Nazer, Lama H.

AU - Tran, Tri M.

AU - Nguyen, Austin

AU - Le, Jennifer

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N2 - Objectives: The objectives of this study were to: 1) evaluate the prevalence of augmented renal clearance in critically ill pediatric patients using vancomycin clearance; 2) derive the pharmacokinetic model that best describes vancomycin clearance in critically ill pediatric patients; and 3) correlate vancomycin clearance with creatinine clearance estimated by modified Schwartz or Cockcroft-Gault. Design: Retrospective, two-center, cohort study from 2003 to 2016. Setting: Clinical drug monitoring services in the PICUs at two tertiary care, teaching hospitals. Patients: Children from 1 to 21 years old. Interventions: None. Measurements and Main Results: Identify patients with augmented renal clearance (vancomycin clearance ≥ 130 mL/min/1.73 m2 used as definition of augmented renal clearance). Derive final population-based pharmacokinetic model and estimate individual patient pharmacokinetic parameters. Compare estimated glomerular filtration rate (modified Schwartz or Cockcroft-Gault depending on age < or ≥ 17 yr) with vancomycin clearance. Augmented renal clearance was identified in 12% of 250 total subjects. The final population-based pharmacokinetic model for vancomycin clearance (L/hr) was 0.118 × weight (e-1.13 × [serum creatinine (Scr)-0.40]). Median vancomycin clearance in those with versus without augmented renal clearance were 141.3 and 91.7 mL/min/1.73 m2, respectively (p < 0.001). By classification and regression tree analysis, patients who were more than 7.9 years old were significantly more likely to experience augmented renal clearance (17% vs 4.6% in those ≤ 7.9 yr old; p = 0.002). In patients with augmented renal clearance, 79% of 29 had vancomycin trough concentrations less than 10 μg/mL, compared with 52% of 221 in those without augmented renal clearance (p < 0.001). Vancomycin clearance was weakly correlated to the glomerular filtration rate estimated by the modified Schwartz or Cockcroft-Gault method (Spearman R2 = 0.083). Conclusions: Augmented renal clearance was identified in one of 10 critically ill pediatric patients using vancomycin clearance, with an increase of approximately 50 mL/min/1.73 m2 in those with augmented renal clearance. As augmented renal clearance results in subtherapeutic antibiotic concentrations, optimal dosing is essential in those exhibiting augmented renal clearance.

AB - Objectives: The objectives of this study were to: 1) evaluate the prevalence of augmented renal clearance in critically ill pediatric patients using vancomycin clearance; 2) derive the pharmacokinetic model that best describes vancomycin clearance in critically ill pediatric patients; and 3) correlate vancomycin clearance with creatinine clearance estimated by modified Schwartz or Cockcroft-Gault. Design: Retrospective, two-center, cohort study from 2003 to 2016. Setting: Clinical drug monitoring services in the PICUs at two tertiary care, teaching hospitals. Patients: Children from 1 to 21 years old. Interventions: None. Measurements and Main Results: Identify patients with augmented renal clearance (vancomycin clearance ≥ 130 mL/min/1.73 m2 used as definition of augmented renal clearance). Derive final population-based pharmacokinetic model and estimate individual patient pharmacokinetic parameters. Compare estimated glomerular filtration rate (modified Schwartz or Cockcroft-Gault depending on age < or ≥ 17 yr) with vancomycin clearance. Augmented renal clearance was identified in 12% of 250 total subjects. The final population-based pharmacokinetic model for vancomycin clearance (L/hr) was 0.118 × weight (e-1.13 × [serum creatinine (Scr)-0.40]). Median vancomycin clearance in those with versus without augmented renal clearance were 141.3 and 91.7 mL/min/1.73 m2, respectively (p < 0.001). By classification and regression tree analysis, patients who were more than 7.9 years old were significantly more likely to experience augmented renal clearance (17% vs 4.6% in those ≤ 7.9 yr old; p = 0.002). In patients with augmented renal clearance, 79% of 29 had vancomycin trough concentrations less than 10 μg/mL, compared with 52% of 221 in those without augmented renal clearance (p < 0.001). Vancomycin clearance was weakly correlated to the glomerular filtration rate estimated by the modified Schwartz or Cockcroft-Gault method (Spearman R2 = 0.083). Conclusions: Augmented renal clearance was identified in one of 10 critically ill pediatric patients using vancomycin clearance, with an increase of approximately 50 mL/min/1.73 m2 in those with augmented renal clearance. As augmented renal clearance results in subtherapeutic antibiotic concentrations, optimal dosing is essential in those exhibiting augmented renal clearance.

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