Development of a preclinical model of ICU-associated sleep fragmentation and effects on pneumonia recovery in mice.

Abstract

Patients in the intensive care unit (ICU) experience many ICU-specific factors that could impact their outcomes apart from their underlying acute illness. The precise function of sleep is not clear, but its importance is suggested by the literature on the deleterious effects of poor sleep and sleep deprivation and may represent a modifiable opportunity in ICU patients. Investigation into the role of sleep in critical illness is impeded by a lack of sufficient murine models. Although many murine models of sleep disruption exist, these do not replicate the ICU patient experience. We modified a traditional model of sleep fragmentation, that is, intermittent orbital shaking, with increased duration and intensity of shaking, and 2-h on and 2-h off light/dark cycles to create an ICU-associated sleep fragmentation model. Continuous electroencephalogram analyses identified significantly reduced total sleep time, significantly fragmented sleep, and a loss of the diurnal sleep-wake cycle in mice exposed to the ICU sleep fragmentation protocol, but not in mice exposed to a traditional sleep fragmentation protocol when compared with baseline conditions. Using a Streptococcus pneumoniae murine model of pneumonia to mimic critical illness, we note a delay in resolution of markers of lung injury in mice exposed to the ICU sleep fragmentation protocol when compared with S. pneumoniae alone. We conclude that traditional sleep fragmentation models may not recapitulate the ICU patient sleep experience. Investigators could use this ICU sleep fragmentation model for mechanistic studies of how sleep disruption in the ICU affects critical illness outcomes.NEW & NOTEWORTHY The study of sleep and its interaction with critical illness has been limited partly due to a paucity of representative models. We developed an ICU-associated sleep fragmentation model that recapitulates many of the key features of sleep experienced by patients in the intensive care unit. Furthermore, we observed delayed recovery in lung injury in an S. pneumoniae murine model when exposed to ICU sleep fragmentation.