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Introduction  Sedative and analgesic medications are routinely used in mechanically ventilated patients. The aim of this review is to discus epidemiologic data that suggest a relationship between infection and sedation, to review available data for the potential causes and pathophysiology of this relationship, and to identify potential preventive measures.    Methods  Data for this review were identified through searches of PubMed, and from bibliographies of relevant articles.    Results  Several epidemiologic studies suggested a link between sedation and ICU-acquired infection. Prolongation of exposure to risk factors for infection, microaspiration, gastrointestinal motility disturbances, microcirculatory effects are main mechanisms by which sedation may favour infection in critically ill patients. Furthermore, experimental evidence coming from studies both in humans and animals suggest that sedatives and analgesics present immunomodulatory properties that might alter the immunologic response to exogenous stimuli. Clinical studies comparing different sedative agents do not provide evidence to recommend the use of a particular agent to reduce ICU-acquired infection rate. However, sedation strategies aiming to reduce the duration of mechanical ventilation, such as daily interruption of sedatives or nursing-implementing sedation protocol, should be promoted. In addition, the use of short acting opioids, propofol, and dexmedetomidine is associated with shorter duration of mechanical ventilation and ICU stay, and might be helpful in reducing ICU-acquired infection rates.    Conclusions  Prolongation of exposure to risk factors for infection, microaspiration, gastrointestinal motility disturbances, microcirculatory effects, and immunomodulatory effects are main mechanisms by which sedation may favour infection in critically ill patients. Future studies should compare the effect of different sedative agents, and the impact of progressive opioid discontinuation compared with abrupt discontinuation on ICU-acquired infection rates.

Intensive care unit-acquired infection as a side effect of sedation