Headley A S, Tolley E, Meduri G U
Department of Medicine, University of Tennessee Medical Center, Memphis, USA.
Chest. 1997 May;111(5):1306-21. doi: 10.1378/chest.111.5.1306.
Systemic inflammatory response syndrome (SIRS) and infections are frequently associated with the development and progression of acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). We investigated, at onset and during the progression of ARDS, the relationships among (1) clinical variables and biological markers of SIRS, (2) infections defined by strict criteria, and (3) patient outcome. Biological markers of SIRS included serial measurements of inflammatory cytokines (IC)-tumor necrosis factor-alpha (TNF-alpha) and interleukins (IL) 1 beta, 2, 4, 6, and 8-in plasma and BAL fluid.
We prospectively studied two groups of ARDS patients: 34 patients treated conventionally (group 1) and nine patients who received glucocorticoid rescue treatment for unresolving ARDS (group 2). Individual SIRS criteria and SIRS composite score were recorded daily for all patients. Plasma IC levels were measured by enzyme-linked immunosorbent assay on days 1, 2, 3, 5, 7, 10, and 12 of ARDS and every third day thereafter while patients received mechanical ventilation. Unless contraindicated, bilateral BAL was performed on day 1, weekly, and when ventilator-associated pneumonia was suspected. Patients were closely monitored for the development of nosocomial infections (NIs).
ICU mortality was similar among patients with and without sepsis on admission (54% vs 40%; p < 0.45). Among patients with sepsis-induced ARDS, mortality was higher in those who subsequently developed NIs (71% vs 18%; p < 0.05). At the onset of ARDS, plasma TNF-alpha, IL-1 beta, IL-6, and IL-8 levels were significantly higher (p < 0.0001) in nonsurvivors (NS) and in those with sepsis (p < 0.0001). The NS group, contrary to survivors (S), had persistently elevated plasma IC levels over time. In 17 patients, 36 definitive NIs (17 in group 1 and 19 in group 2) were diagnosed by strict criteria. No definitive or presumed NIs caused an increase in plasma IC levels above patients' preinfection baseline. Daily SIRS components and SIRS composite scores were similar among S and NS and among patients with and without sepsis-induced ARDS, were unaffected by the development of NI, and did not correlate with plasma IC levels.
Sepsis as a precipitating cause of ARDS was associated with higher plasma IC levels. However, NIs were not associated with an increase in SIRS composite scores, individual SIRS criteria, or plasma IC levels above patients' preinfection baseline. SIRS composite scores over time were similar in S and NS. SIRS criteria, including fever, were found to be nonspecific for NI. Irrespective of etiology of ARDS, plasma IC levels, but not clinical criteria, correlated with patient outcome. These findings suggest that final outcome in patients with ARDS is related to the magnitude and duration of the host inflammatory response and is independent of the precipitating cause of ARDS or the development of intercurrent NIs.
全身炎症反应综合征（SIRS）和感染常与急性呼吸窘迫综合征（ARDS）及多器官功能障碍综合征（MODS）的发生和发展相关。我们在ARDS发病时及病程中，研究了以下三者之间的关系：（1）SIRS的临床变量和生物学标志物；（2）严格标准定义的感染；（3）患者预后。SIRS的生物学标志物包括血浆和支气管肺泡灌洗（BAL）液中炎症细胞因子（IC）——肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）-1β、2、4、6及8的系列测量值。
我们前瞻性地研究了两组ARDS患者：34例接受常规治疗的患者（第1组）和9例因ARDS未缓解而接受糖皮质激素挽救治疗的患者（第2组）。每天记录所有患者的个体SIRS标准和SIRS综合评分。在ARDS的第1、2、3、5、7、10和12天以及此后每隔三天患者接受机械通气时，通过酶联免疫吸附测定法测量血浆IC水平。除非有禁忌证，在第1天、每周以及怀疑有呼吸机相关性肺炎时进行双侧BAL。密切监测患者医院感染（NI）的发生情况。
入院时伴有和不伴有脓毒症的患者的重症监护病房（ICU）死亡率相似（54%对40%；p<0.45）。在脓毒症诱发ARDS的患者中，随后发生NI的患者死亡率更高（71%对18%；p<0.05）。在ARDS发病时，非幸存者（NS）和脓毒症患者的血浆TNF-α、IL-1β、IL-6和IL-8水平显著更高（p<0.0001）。与幸存者（S）相反，NS组血浆IC水平随时间持续升高。通过严格标准诊断出17例患者有36例明确的NI（第1组17例，第2组19例）。没有明确的或疑似的NI导致血浆IC水平升高超过患者感染前基线。S组和NS组之间以及伴有和不伴有脓毒症诱发ARDS的患者之间，每日SIRS成分和SIRS综合评分相似，不受NI发生的影响，且与血浆IC水平无关。
脓毒症作为ARDS的促发原因与较高的血浆IC水平相关。然而，NI与SIRS综合评分、个体SIRS标准或血浆IC水平升高超过患者感染前基线无关。S组和NS组随时间推移的SIRS综合评分相似。包括发热在内的SIRS标准被发现对NI不具有特异性。无论ARDS的病因如何，血浆IC水平而非临床标准与患者预后相关。这些发现表明，ARDS患者的最终预后与宿主炎症反应的程度和持续时间有关，且独立于ARDS的促发原因或并发NI的发生。
