Cohen Mitchell J, Bir Natasha, Rahn Pamela, Dotson Rachel, Brohi Karim, Chesebro Brian B, Mackersie Robert, Carles Michel, Wiener-Kronish Jeanine, Pittet Jean-François
Department of Surgery, University of California, San Francisco, California, USA.
J Trauma. 2009 Dec;67(6):1176-81. doi: 10.1097/TA.0b013e3181c1c1bc.
Mechanically ventilated trauma patients have a high risk for the development of ventilator-associated pneumonia (VAP). We have recently reported that reduced plasma protein C (PC) levels early after trauma/shock are associated with coagulopathy and mortality. Furthermore, trauma patients with tissue injury and shock are at higher risk for the development of VAP.
We hypothesized that low PC levels early after trauma are associated with an increased susceptibility to VAP in trauma patients.
Fifty-nine acutely injured, intubated trauma patients were admitted to the critical care unit. Serial blood samples were drawn and coagulation factors were measured. VAP was diagnosed by presence of bacteria on bronchial alveolar lavage specimen, bilateral infiltrates on chest roentgenogram, and fever or elevated white blood cell count.
There were no differences in demographic or injury characteristics between patients who developed VAP and those who did not. As expected, patients who developed VAP had more ventilator days, hospital days, intensive care unit days, and greater mortality (all p < 0.05). Patients in both groups had lower mean PC levels at 6 hours compared with baseline. Noninfected patients' PC subsequently returned to near baseline levels, whereas those patients who eventually acquired VAP had significantly lower PC levels at both 12 and 24 hours (12 hours: 79 vs. 96%, p = 0.05; 24 hours: 75 vs. 97% p = 0.02). Soluble endothelial PC receptor (sEPCR) levels were also lower at 24 hours (82 vs. 99% in the noninfected group, p = 0.04).
The activation of PC pathway early after trauma may protect the vascular endothelium by both its anticoagulant and cytoprotective effects. However, trauma patients who later developed VAP have significantly lower plasma levels of PC within 24 hours after injury, suggesting a possible consumption of this vitamin K-dependent protein and an inhibition of its activation by inflammatory mediators. EPCR is involved in the activation of PC and is also a mediator of its cytoprotective effects.
Critically ill trauma patients have an early activation of the PC pathway, associated with a rapid decrease in the plasma levels of this protein and increase in EPCR. Plasma levels of PC return to normal levels within 24 hours in most patients. However, patients who go on to acquire VAP have persistently low plasma levels of PC in the immediate period after trauma. Whether PC could play a mechanistic role in the host response against nosocomial lung infection warrants further study.
机械通气的创伤患者发生呼吸机相关性肺炎（VAP）的风险很高。我们最近报道，创伤/休克后早期血浆蛋白C（PC）水平降低与凝血病和死亡率相关。此外，伴有组织损伤和休克的创伤患者发生VAP的风险更高。
我们假设创伤后早期低PC水平与创伤患者发生VAP的易感性增加有关。
59例急性受伤、插管的创伤患者入住重症监护病房。采集系列血样并检测凝血因子。通过支气管肺泡灌洗标本中存在细菌、胸部X线片显示双侧浸润以及发热或白细胞计数升高来诊断VAP。
发生VAP的患者与未发生VAP的患者在人口统计学或损伤特征方面无差异。正如预期的那样，发生VAP的患者有更多的机械通气天数、住院天数、重症监护病房天数，且死亡率更高（所有p<0.05）。与基线相比，两组患者在6小时时的平均PC水平均较低。未感染患者PC随后恢复至接近基线水平，而最终发生VAP的患者在12小时和24小时时的PC水平均显著较低（12小时：79%对96%，p=0.05；24小时：75%对97%，p=0.02）。可溶性内皮PC受体（sEPCR）水平在24小时时也较低（未感染组为82%对99%，p=0.04）。
创伤后早期PC途径的激活可能通过其抗凝和细胞保护作用来保护血管内皮。然而，后来发生VAP的创伤患者在受伤后24小时内血浆PC水平显著较低，提示这种维生素K依赖性蛋白可能被消耗，且其激活受到炎症介质的抑制。EPCR参与PC的激活，也是其细胞保护作用的介质。
重症创伤患者PC途径早期激活，伴随着该蛋白血浆水平迅速下降和EPCR升高。大多数患者血浆PC水平在24小时内恢复正常水平。然而，发生VAP的患者在创伤后短期内血浆PC水平持续较低。PC是否能在宿主对抗医院获得性肺部感染的反应中发挥机制性作用值得进一步研究。
