Clinical studies to investigate pharmacokinetics of antimicrobial agents in critically ill patients

markdownabstract__Abstract__ The intensive care unit (ICU) is an essential part of the surgical department, providing an environment for surveillance and treatment of the critically ill. Patients are admitted either with a life threatening condition due to a critical illness or they need observation and support after major surgery. In the Netherlands, approximately 60.000 patients are admitted to an adult ICU annually, which is 4% of total number of hospital admissions (Prismant 2002, Utrecht). Infections are common in surgical ICU patients. An incidence of up to 40% of all admissions has been reported. Infections are a major indication for admission as in patients with generalised peritonitis or respiratory insufficiency due to a postoperative pneumonia. Furthermore, patients admitted for extensive trauma or after major surgery are susceptible to infectious complications. The host defences of the surgical patient are compromised by both extrinsic and intrinsic factors. Normal barriers are breached by surgical incisions and by intravascular lines, wound drains, urinary catheters and endotracheal tubes. The integrity of the gastrointestinal epithelium is compromised by lack of enteral nutrition and periods of hypoperfusion, promoting bacterial translocation. The protective indigenous microbial flora is changed by the use of broad-spectrum antibiotics. Furthermore, multiple alterations in the systemic immunity are seen. Natural downregulatory mechanisms for the inflammatory response exist, probably to limit autoimmune damage. Iatrogenic immune suppression is applied frequently following organ transplantation or with corticosteroids in pulmonary dysfunction. At last, there are preexistent diseases associated with impaired host defences, including cirrhosis, renal failure, malignancy and diabetes