Friese Randall S, Bruns Brandon, Sinton Christopher M
Division of Trauma Critical Care and Emergency Surgery, Department of Surgery, College of Medicine, University of Arizona, Tucson, Arizona 85724-5063, USA.
J Trauma. 2009 Jan;66(1):50-4. doi: 10.1097/TA.0b013e318190c3a1.
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.
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.
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).
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.
睡眠剥夺是重症监护病房中的常见问题。动物模型已表明，单纯睡眠剥夺与死亡率增加有关。我们之前已经表明，脓毒症损伤合并睡眠剥夺会导致小鼠模型死亡率增加。众所周知，衰老过程会减少睡眠的恢复阶段。本研究的目的是评估年龄对脓毒症损伤恢复期间睡眠剥夺所致死亡率的影响。
将2个月龄（年轻）或9个月龄（年老）的C57BL/6J雄性小鼠进行盲肠结扎和穿刺（CLP）。动物被随机分为接受48小时睡眠中断（SI）或标准恢复（无SI）。假手术动物进行剖腹术和盲肠操作但不穿刺。通过将动物饲养箱固定在设置为以30转/分钟反复循环120秒（开30秒/关90秒）的轨道振荡器上来实现SI。主要结局是CLP后5天的生存率。采用Kaplan-Meier生存分析和对数秩检验来探讨死亡率的差异。
SI导致光周期和暗周期的清醒时间均增加（p<0.001）。CLP合并SI组（n = 30）的死亡率为57%，CLP无SI组（对照组；n = 33）的死亡率为24%。SI与CLP后死亡率增加超过3倍相关（RR = 3.29；95%CI，1.42 - 7.63）。年轻小鼠（n = 28）单独CLP的死亡率为31%，合并SI时增至67%（p = 0.03）。年老小鼠（n = 35）单独CLP的死亡率为18%，合并SI时增至50%（p = 0.05）。接受SI的年轻和年老小鼠的生存率无差异（p = 0.49）。
脓毒症损伤后的睡眠剥夺会增加年轻和年老小鼠的死亡率。然而，脓毒症损伤后的睡眠剥夺对两个年龄组的死亡率影响均不更显著。这些发现表明，重症疾病恢复期间在重症监护病房环境中经历的睡眠剥夺可能会增加死亡率。这种影响似乎与年龄增长无关。有必要进一步开展评估极端年龄情况的研究。
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