OBJECTIVES: 

To test the hypothesis that forced-air warming of critically ill afebrile sepsis patients improves immune function compared to standard temperature management.

DESIGN: 

Single-center, prospective, open-label, randomized controlled trial.

SETTING: 

One thousand two hundred-bed academic medical center.

PATIENTS: 

Eligible patients were mechanically ventilated septic adults with: 1) a diagnosis of sepsis within 48 hours of enrollment; 2) anticipated need for mechanical ventilation of greater than 48 hours; and 3) a maximum temperature less than 38.3°C within the 24 hours prior to enrollment. Primary exclusion criteria included: immunologic diseases, immune-suppressing medications, and any existing condition sensitive to therapeutic hyperthermia (e.g., brain injury). The primary outcome was monocyte human leukocyte antigen (HLA)-DR expression, with secondary outcomes of CD3/CD28-induced interferon gamma (IFN-γ) production, mortality, and 28-day hospital-free days.

INTERVENTIONS: 

External warming using a forced-air warming blanket for 48 hours, with a goal temperature 1.5°C above the lowest temperature documented in the previous 24 hours.

MEASUREMENTS AND MAIN RESULTS: 

We enrolled 56 participants in the study. No differences were observed between the groups in HLA-DR expression (692 vs 2,002; p = 0.396) or IFN-γ production (31 vs 69; p = 0.678). Participants allocated to external warming had lower 28-day mortality (18% vs 43%; absolute risk reduction, 25%; 95% CI, 2–48%) and more 28-day hospital-free days (difference, 2.6 d; 95% CI, 0–11.6).

CONCLUSIONS: 

Participants randomized to external forced-air warming did not have a difference in HLA-DR expression or IFN-γ production. In this pilot study, however, 28-day mortality was lower in the intervention group. Future research should seek to better elucidate the impact of temperature modulation on immune and nonimmune organ failure pathways in sepsis.

中文翻译：

---

治疗性热疗与脓毒症无发热重症患者生存率的提高相关：一项随机试验

 目标：

检验以下假设：与标准温度管理相比，危重无热脓毒症患者的强制空气加温可改善免疫功能。

 设计：

单中心、前瞻性、开放标签、随机对照试验。

 环境：

拥有一千二百个床位的学术医疗中心。

 患者：

符合条件的患者是机械通气脓毒症成人，且满足以下条件： 1) 在入组后 48 小时内诊断为脓毒症； 2) 预期需要机械通气超过 48 小时； 3) 入学前24小时内最高体温低于38.3°C。主要排除标准包括：免疫性疾病、免疫抑制药物以及任何对热疗敏感的现有病症（例如脑损伤）。主要结果是单核细胞人类白细胞抗原 (HLA)-DR 表达，次要结果是 CD3/CD28 诱导的干扰素 γ (IFN-γ) 产生、死亡率和 28 天无住院天数。

 干预措施：

使用强制通风保暖毯进行外部保暖 48 小时，目标温度比前 24 小时内记录的最低温度高 1.5°C。

测量和主要结果：

我们招募了 56 名参与者参加这项研究。各组之间的 HLA-DR 表达（692 vs 2,002； p = 0.396）或 IFN-γ 产量（31 vs 69； p = 0.678）没有观察到差异。分配到外部变暖的参与者的 28 天死亡率较低（18% vs 43%；绝对风险降低，25%；95% CI，2-48%），并且 28 天无需住院天数较多（差异为 2.6 天；95 % CI，0–11.6）。

 结论：

随机接受外部强制空气加温的参与者在 HLA-DR 表达或 IFN-γ 产生方面没有差异。然而，在这项试点研究中，干预组的 28 天死亡率较低。未来的研究应该寻求更好地阐明温度调节对脓毒症免疫和非免疫器官衰竭途径的影响。