Table 2.

Mechanisms by which sedation might promote ICU-acquired infection

Mechanism	References	Study design/Number of patients	Main results
Prolongation of exposure to risk factors
Longer duration of mechanical ventilation, and ICU stay	[17,23]	Prospective cohorts/5183, and 252; respectively	Durations of mechanical ventilation and ICU stay significantly longer in patients receiving sedation compared with those without sedation
Microaspiration
Neurologic impairment	[23]	Prospective cohort/360	Heavy sedation significantly associated with microaspiration confirmed by pepsin-positive tracheal aspirate
Impaired tubular esophageal motility	[34]	Prospective cohort/21	Esophageal motility significantly reduced in sedated patients compared to healthy controls
Microcirculatory disturbances	[35]	Prospective cohort/10	Sedation induced an increase in cutaneous blood flow, a decrease in reactive hyperemia, and alterations of vasomotions
Gastrointestinal motility disturbances
Opioids	[40]	Double-blind, placebo-controlled, randomized study comparing the effects of lactulose, polyethylene glycol, or placebo on defecation/308	Morphine administration associated with a longer time before first defecation, except in the polyethylene glycol group
Dexmedetomidine and clonidine	[47]	Animal study/NA	Clonidine and dexmedetomidine concentration-dependently increased peristaltic pressure threshold and inhibited peristalsis
Immunomodulatory effects	-	-	Please see Table 3 for details

ICU: intensive care unit; NA: not applicable.