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The effect of pathophysiology on pharmacokinetics in the critically ill patient : concepts appraised by the example of antimicrobial agents

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Abstract
Critically ill patients are at high risk for development of life-threatening infection leading to sepsis and multiple organ failure. Adequate antimicrobial therapy is pivotal for optimizing the chances of survival. However, efficient dosing is problematic because pathophysiological changes associated with critical illness impact on pharmacokinetics of mainly hydrophilic antimicrobials. Concentrations of hydrophilic antimicrobials may be increased because of decreased renal clearance due to acute kidney injury. Alternatively, antimicrobial concentrations may be decreased because of increased volume of distribution and augmented renal clearance provoked by systemic inflammatory response syndrome, capillary leak, decreased protein binding and administration of intravenous fluids and inotropes. Often multiple conditions that may influence pharmacokinetics are present at the same time thereby excessively complicating the prediction of adequate concentrations. In general, conditions leading to underdosing are predominant. Yet, since prediction of serum concentrations remains difficult, therapeutic drug monitoring for individual fine-tuning of antimicrobial therapy seems the way forward.
Keywords
Pharmacokinetics, Antimicrobial agents, Pharmacodynamics, Intensive care unit, Sepsis, Organ failure, Acute kidney injury, Hepatic failure, RENAL REPLACEMENT THERAPY, INTENSIVE-CARE-UNIT, ACUTE KIDNEY INJURY, STAPHYLOCOCCUS-AUREUS BACTEREMIA, ORGAN BLOOD-FLOW, SEPTIC SHOCK, SEVERE SEPSIS, CONTINUOUS-INFUSION, ATTRIBUTABLE MORTALITY, NOSOCOMIAL INFECTION

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Chicago
Blot, Stijn, Federico Pea, and Jeffrey Lipman. 2014. “The Effect of Pathophysiology on Pharmacokinetics in the Critically Ill Patient : Concepts Appraised by the Example of Antimicrobial Agents.” Advanced Drug Delivery Reviews 77: 3–11.
APA
Blot, S., Pea, F., & Lipman, J. (2014). The effect of pathophysiology on pharmacokinetics in the critically ill patient : concepts appraised by the example of antimicrobial agents. ADVANCED DRUG DELIVERY REVIEWS, 77, 3–11.
Vancouver
1.
Blot S, Pea F, Lipman J. The effect of pathophysiology on pharmacokinetics in the critically ill patient : concepts appraised by the example of antimicrobial agents. ADVANCED DRUG DELIVERY REVIEWS. 2014;77:3–11.
MLA
Blot, Stijn, Federico Pea, and Jeffrey Lipman. “The Effect of Pathophysiology on Pharmacokinetics in the Critically Ill Patient : Concepts Appraised by the Example of Antimicrobial Agents.” ADVANCED DRUG DELIVERY REVIEWS 77 (2014): 3–11. Print.
@article{4239801,
  abstract     = {Critically ill patients are at high risk for development of life-threatening infection leading to sepsis and multiple organ failure. Adequate antimicrobial therapy is pivotal for optimizing the chances of survival. However, efficient dosing is problematic because pathophysiological changes associated with critical illness impact on pharmacokinetics of mainly hydrophilic antimicrobials. Concentrations of hydrophilic antimicrobials may be increased because of decreased renal clearance due to acute kidney injury. Alternatively, antimicrobial concentrations may be decreased because of increased volume of distribution and augmented renal clearance provoked by systemic inflammatory response syndrome, capillary leak, decreased protein binding and administration of intravenous fluids and inotropes. Often multiple conditions that may influence pharmacokinetics are present at the same time thereby excessively complicating the prediction of adequate concentrations. In general, conditions leading to underdosing are predominant. Yet, since prediction of serum concentrations remains difficult, therapeutic drug monitoring for individual fine-tuning of antimicrobial therapy seems the way forward.},
  author       = {Blot, Stijn and Pea, Federico and Lipman, Jeffrey},
  issn         = {0169-409X},
  journal      = {ADVANCED DRUG DELIVERY REVIEWS},
  keyword      = {Pharmacokinetics,Antimicrobial agents,Pharmacodynamics,Intensive care unit,Sepsis,Organ failure,Acute kidney injury,Hepatic failure,RENAL REPLACEMENT THERAPY,INTENSIVE-CARE-UNIT,ACUTE KIDNEY INJURY,STAPHYLOCOCCUS-AUREUS BACTEREMIA,ORGAN BLOOD-FLOW,SEPTIC SHOCK,SEVERE SEPSIS,CONTINUOUS-INFUSION,ATTRIBUTABLE MORTALITY,NOSOCOMIAL INFECTION},
  language     = {eng},
  pages        = {3--11},
  title        = {The effect of pathophysiology on pharmacokinetics in the critically ill patient : concepts appraised by the example of antimicrobial agents},
  url          = {http://dx.doi.org/10.1016/j.addr.2014.07.006},
  volume       = {77},
  year         = {2014},
}

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