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 from literature of 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 lack of sufficient murine models. While many murine models of sleep disruption exist, these do not replicate the ICU patient experience. We modified a traditional model of sleep fragmentation, i.e. intermittent orbital shaking, with increased duration and intensity of shaking, and 2hr on and 2hr off light/dark cycles to create a 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 to baseline conditions. Using a S. 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 to S. pneumoniae alone. We conclude that traditional sleep fragmentation models may not recapitulate the ICU patient sleep experience. Investigators could employ this ICU sleep fragmentation model for mechanistic studies of how sleep disruption in the ICU affects critical illness outcomes.