J T Kielstein1. 1. Klinik für Nieren- und Hochdruckerkrankungen, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland, kielstein@yahoo.com.
Abstract
BACKGROUND: The dosing of drugs in critically ill patients remains challenging. While increased volume of distribution after fluid resuscitation and increased cardiac output can increase clearance of antibiotics, liver failure and renal failure can decrease the clearance of drugs. If an extracorporeal device is used, the dosing of drugs becomes even more difficult. Even in intensive care patients with intact renal function, pharmacokinetics and pharmacodynamics are significantly altered. CURRENT SITUATION: While there are direct readouts such as the mean arterial pressure for catecholamine therapy and measurement of serum glucose to guide insulin dosing, we lack such prompt readouts for dosing of antibiotics. In this manuscript, the principles and basic knowledge needed to improve dosing of anti-infective agents in critically ill patients undergoing extracorporeal treatment are described. Examples are the rapid utility assessment drug dosing reference books and online resources including the vancomycin test. Potential problems of extracorporeal membrane oxygenation and adsober therapy associated with renal replacement therapy are also addressed. CONCLUSION: The importance of therapeutic drug monitoring is discussed. Global initiatives to increase quantity and quality of pharmacokinetic studies in this patient population through incentives and guidance of the regulatory agencies, as well as the major unmet educational need to integrate basic knowledge in this field into residency and fellowship programs as well as CME are briefly mentioned.
BACKGROUND: The dosing of drugs in critically illpatients remains challenging. While increased volume of distribution after fluid resuscitation and increased cardiac output can increase clearance of antibiotics, liver failure and renal failure can decrease the clearance of drugs. If an extracorporeal device is used, the dosing of drugs becomes even more difficult. Even in intensive care patients with intact renal function, pharmacokinetics and pharmacodynamics are significantly altered. CURRENT SITUATION: While there are direct readouts such as the mean arterial pressure for catecholamine therapy and measurement of serum glucose to guide insulin dosing, we lack such prompt readouts for dosing of antibiotics. In this manuscript, the principles and basic knowledge needed to improve dosing of anti-infective agents in critically illpatients undergoing extracorporeal treatment are described. Examples are the rapid utility assessment drug dosing reference books and online resources including the vancomycin test. Potential problems of extracorporeal membrane oxygenation and adsober therapy associated with renal replacement therapy are also addressed. CONCLUSION: The importance of therapeutic drug monitoring is discussed. Global initiatives to increase quantity and quality of pharmacokinetic studies in this patient population through incentives and guidance of the regulatory agencies, as well as the major unmet educational need to integrate basic knowledge in this field into residency and fellowship programs as well as CME are briefly mentioned.
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