Sleep deprivation after septic insult increases mortality independent of age.

Abstract

BACKGROUND Sleep deprivation is a common problem in the intensive care unit. Animal models have demonstrated that sleep deprivation alone is associated with increased mortality. We have previously shown that septic insult with sleep deprivation results in increased mortality in a murine model. The aging process is known to reduce the restorative phases of sleep. The purpose of this study was to evaluate the effect of age on mortality with sleep deprivation during recovery from septic insult. METHODS C57BL/6J male mice aged 2 months (young) or 9 months (old) underwent cecal ligation and puncture (CLP). Animals were randomized to receive sleep interruption (SI) for 48 hours or standard recovery (no SI). Sham animals underwent laparotomy and cecal manipulation without puncture. SI was achieved by securing animal housing to an orbital shaker set to repeatedly cycle at 30 rpm over 120 seconds (30 seconds on/90 seconds off). The primary outcome was survival at 5 days post-CLP. Kaplan-Meier survival analysis with log-rank test was used to explore differences in mortality. RESULTS SI resulted in an increase in time awake for both light and dark cycles (p < 0.001). Mortality after CLP with SI (n = 30) was 57% and mortality after CLP without SI (controls; n = 33) was 24%. SI was associated with a greater than 3-fold increase in mortality after CLP (RR = 3.29; 95% CI, 1.42-7.63). Young mice (n = 28) had a mortality of 31% with CLP alone increasing to 67% with SI (p = 0.03). Old mice (n = 35) had a mortality of 18% with CLP alone increasing to 50% with SI (p = 0.05). There was no difference in survival between young and old mice undergoing SI (p = 0.49). CONCLUSIONS Sleep deprivation after septic insult increases mortality in both young and old mice. However, sleep deprivation after septic insult does not have a more profound effect on mortality in either age group. These findings suggest that sleep deprivation experienced in the intensive care unit setting during recovery from critical illness may increase mortality. This effect appears independent of increased age. Further studies evaluating extremes of age are warranted.