Pinsky M R, Vincent J L, Deviere J, Alegre M, Kahn R J, Dupont E
Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh.
Chest. 1993 Feb;103(2):565-75. doi: 10.1378/chest.103.2.565.
Cytokines have been associated with the development of sepsis and diffuse tissue injury following septic or endotoxic challenges in humans. Furthermore, relative organ-system dysfunction, not specific organ dysfunction, appears to predict outcome from critical illness. We hypothesized that persistence of inflammatory cytokines within the circulation, reflecting a generalized systemic inflammatory response, is associated with multiple-system organ failure (MSOF) and death from critical illness. In addition, since hepatic function is central to host-defense homeostasis, we further reasoned that critically ill patients with hepatic cirrhosis would have an increased incidence of MSOF and death following sepsis associated with a persistence of cytokines in the blood.
We measured serum levels of tumor necrosis factor (TNF), interleukin (IL) 1, IL-2, IL-6, and interferon gamma (IFG) serially for the first 48 h following the onset of hypotension (systolic blood pressure < 90 mm Hg) thought likely to be due to sepsis in all patients presenting to one ICU. These data were correlated with initial severity of shock and retrospective determination of septic or nonseptic origin, preexistent hepatic cirrhosis, subsequent development of MSOF, and outcome.
Fifty-three specific episodes of shock in 52 patients were recorded (35 septic and 18 nonseptic episodes). Mortality was higher in septic patients (41 vs 17 percent, p < 0.01), as was the development of MSOF (29 vs 6 percent, p < 0.001), incidence of cirrhosis (21 vs 0 percent, p < 0.01), and TNF levels over the study interval (p < 0.01). Nonseptic patients also had an initial elevation in TNF over 48-h levels (p < 0.05) that were higher than serum levels reported for normal subjects (chi 2, p < 0.05). There was no relation between peak TNF level and outcome. Sixty-seven percent of the cirrhotic patients had development of MSOF and died, while only 30 percent of the noncirrhotic patients had development of MSOF or died (p < 0.05). The TNF and IL-6 levels in patients who had MSOF or who died were both elevated and did not decrease over time independent of presence or absence of sepsis (p < 0.01). Similarly, IL-6 levels after 12 h were higher in cirrhotic patients than in noncirrhotic septic patients (p < 0.05). No elevation in IL-1, IL-2, or IFG was seen in any patient subpopulation.
TNF and IL-6 serum levels are higher in septic than in nonseptic shock, but the persistence of TNF and IL-6 in the serum rather than peak levels of cytokines predicts a poor outcome in patients with shock.
细胞因子与人类脓毒症及脓毒症或内毒素激发后的弥漫性组织损伤的发生有关。此外，是相对器官系统功能障碍，而非特定器官功能障碍，似乎可预测危重病的预后。我们推测，循环中炎症细胞因子的持续存在反映了全身性炎症反应，与多系统器官衰竭（MSOF）及危重病死亡相关。此外，由于肝功能对宿主防御内环境稳定至关重要，我们进一步推断，肝硬化的危重病患者在脓毒症后发生MSOF及死亡的发生率会增加，且与血液中细胞因子的持续存在有关。
在一所重症监护病房（ICU）就诊的所有患者中，对于发生低血压（收缩压<90mmHg）且推测可能由脓毒症引起的患者，在低血压发作后的头48小时内连续测量血清肿瘤坏死因子（TNF）、白细胞介素（IL）-1、IL-2、IL-6和干扰素γ（IFG）水平。这些数据与休克的初始严重程度、脓毒症或非脓毒症病因的回顾性判定、既往肝硬化情况、随后MSOF的发生及预后相关。
记录了52例患者的53次特定休克发作（35次脓毒症发作和18次非脓毒症发作）。脓毒症患者的死亡率更高（41%对17%，p<0.01），MSOF的发生率也更高（29%对6%，p<0.001），肝硬化的发生率更高（21%对0%，p<0.01），且在研究期间TNF水平更高（p<0.01）。非脓毒症患者在48小时内TNF水平也有初始升高（p<0.05），高于正常受试者报告的血清水平（χ2，p<0.05）。TNF峰值水平与预后无关。67%的肝硬化患者发生了MSOF并死亡，而只有30%的非肝硬化患者发生了MSOF或死亡（p<0.05）。发生MSOF或死亡的患者的TNF和IL-6水平均升高，且不随时间下降，与是否存在脓毒症无关（p<0.01）。同样，12小时后肝硬化患者的IL-6水平高于非肝硬化脓毒症患者（p<0.05）。在任何患者亚组中均未观察到IL-1、IL-2或IFG升高。
脓毒症休克患者的TNF和IL-6血清水平高于非脓毒症休克患者，但血清中TNF和IL-6的持续存在而非细胞因子的峰值水平可预测休克患者的不良预后。
