Cheadle W G, Mercer-Jones M, Heinzelmann M, Polk H C
Department of Surgery and Price Institute of Surgical Research, University of Louisville School of Medicine, Kentucky 40292, USA.
Shock. 1996;6 Suppl 1:S6-9.
The estimation of patients who are at risk for infection, sepsis, and organ dysfunction/failure is crucial not only for inclusion in treatment algorithms but also for entry into appropriate clinical trials of prophylaxis and therapy. Patients on the surgical service who have sustained major trauma or who have undergone transplantation are clearly at the greatest risk. Other immunosuppressed patients at risk for sepsis include those receiving myelosuppressive chemotherapy, those with overwhelming malignancy, and those who suffer from cirrhosis, diabetes mellitus, and severe malnutrition. We have focused on the trauma patient, in whom infection and organ failure are the leading causes of late death, major morbidity, and prolonged hospital stay. Over a 10 yr period, we have surveyed a number of host defense parameters that pertain to an adequate immune response and found a suppressed response shortly after injury in many. All were anergic to a standard skin test panel, and the duration of anergy varied with the clinical course of infection. Immunoglobulin levels were low after major injury as well as specific antibodies to both Gram-positive and Gram-negative organisms. The ability of serum from the trauma patient to opsonize heat-killed bacteria was markedly depressed 24 h after injury in those patients who subsequently died of infection. Class II major histocompatibility antigen expression on peripheral blood monocytes correlated closely with clinical outcome and led to the development of an Outcome Predictive Score. This score can identify patients within hours of hospitalization who are at risk of subsequently developing overt clinical infection and sepsis. Intervention then can be applied to such at-risk populations prior to the onset of sepsis and to evaluate the efficacy of prophylaxis. Patients in whom prophylaxis fails could be eligible for trials of therapeutic intervention as well.
评估有感染、脓毒症及器官功能障碍/衰竭风险的患者不仅对纳入治疗方案至关重要,而且对进入适当的预防和治疗临床试验也很关键。外科手术中遭受重大创伤或接受移植的患者显然风险最大。其他有脓毒症风险的免疫抑制患者包括接受骨髓抑制化疗的患者、患有严重恶性肿瘤的患者以及患有肝硬化、糖尿病和严重营养不良的患者。我们重点关注了创伤患者,在这类患者中,感染和器官衰竭是导致晚期死亡、严重发病和住院时间延长的主要原因。在10年的时间里,我们调查了许多与充分免疫反应相关的宿主防御参数,发现许多患者在受伤后不久免疫反应就受到抑制。所有患者对标准皮肤试验组均无反应,无反应的持续时间随感染的临床过程而变化。重大损伤后免疫球蛋白水平较低,同时针对革兰氏阳性和革兰氏阴性菌的特异性抗体水平也较低。在那些随后死于感染的患者中,创伤患者血清调理热杀死细菌的能力在受伤后24小时明显降低。外周血单核细胞上的II类主要组织相容性抗原表达与临床结果密切相关,并由此开发出了一个结果预测评分。该评分可以在患者住院数小时内识别出有随后发生明显临床感染和脓毒症风险的患者。然后可以在脓毒症发作前对这类高危人群进行干预,并评估预防措施的效果。预防措施失败的患者也有资格参加治疗性干预试验。