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连续性静脉-静脉血液滤过对实验性猪胰腺炎中脓毒症相关免疫麻痹的减轻作用

Attenuation of sepsis-related immunoparalysis by continuous veno-venous hemofiltration in experimental porcine pancreatitis.

作者信息

Yekebas E F, Eisenberger C F, Ohnesorge H, Saalmüller A, Elsner H A, Engelhardt M, Gillesen A, Meins J, The M, Strate T, Busch C, Knoefel W T, Bloechle C, Izbicki J R

机构信息

Department of Surgery, University Hospital Eppendorf, Hamburg, Germany.

出版信息

Crit Care Med. 2001 Jul;29(7):1423-30. doi: 10.1097/00003246-200107000-00021.

DOI:10.1097/00003246-200107000-00021
PMID:11445702
Abstract

OBJECTIVES

In light of evidence suggesting that hemofiltration favorably influences septic diseases by removing sepsis mediators, the impact of different modalities of continuous veno-venous hemofiltration (CVVH) on outcome and immunologic derangements in porcine pancreatogenic sepsis was evaluated.

DESIGN

Randomized, controlled intervention trial.

SUBJECTS

Forty-eight minipigs of either sex.

INTERVENTIONS

Pancreatitis was induced by intraductal injection of sodium taurocholate (4%, 1 mL/kg body weight [BW]) and enterokinase (2 U/kg BW). Animals were allocated either to untreated controls-group 1-or to one of three treatment groups-group 2: low-volume CVVH (20 mL/kg BW), no change of hemofilters; group 3: low-volume CVVH, filters changed every 12 hrs; and group 4: high-volume CVVH (100 mL/kg BW), filters changed every 12 hrs. Survival represented the major parameter of the study. Serum cytokine levels, sepsis-related down-regulation of major histocompatibility complex II and CD14 expression on leukocytes, bacterial translocation, and endotoxemia were further parameters evaluated in the study.

MEASUREMENTS AND MAIN RESULTS

High-volume CVVH combined with periodic filter change was significantly superior compared with less intensive treatment modalities (low-volume CVVH, no filter change) in sepsis protection. Long-term survival (>60 hrs) was found in 67% of group 4 and 33% of group 3 animals (p <.05), whereas in controls and group 2 no animal survived. CVVH ameliorated the initial serum tumor necrosis factor-alpha response and prevented sepsis-induced in vitro endotoxin hyporesponsiveness. Down-regulation of major histocompatibility complex II and CD14 expression on monocytes was significantly improved by CVVH. Improved oxidative burst and phagocytosis capacity in polymorphonuclear leukocytes suggested that leukocyte function was stabilized by CVVH. Also, CVVH significantly reduced bacterial translocation and endotoxemia.

CONCLUSIONS

Hemofiltration reversed sepsis-induced immunoparalysis in a porcine model of bile acid-induced pancreatitis. Implications for human pancreatitis must be validated in prospective, clinical protocols.

摘要

目的

鉴于有证据表明血液滤过通过清除脓毒症介质对脓毒症性疾病产生有益影响,本研究评估了不同模式的连续性静脉-静脉血液滤过(CVVH)对猪源性胰腺炎脓毒症预后及免疫紊乱的影响。

设计

随机对照干预试验。

对象

48只雌雄不限的小型猪。

干预措施

通过导管内注射牛磺胆酸钠(4%,1 mL/kg体重[BW])和肠激酶(2 U/kg BW)诱导胰腺炎。动物被分为未治疗的对照组(第1组)或三个治疗组之一:第2组:小容量CVVH(20 mL/kg BW),滤器不更换;第3组:小容量CVVH,滤器每12小时更换一次;第4组:大容量CVVH(100 mL/kg BW),滤器每12小时更换一次。生存情况是本研究的主要参数。研究中还评估了血清细胞因子水平、脓毒症相关的主要组织相容性复合体II下调以及白细胞上CD14表达、细菌移位和内毒素血症等其他参数。

测量指标及主要结果

与强度较低的治疗模式(小容量CVVH,不更换滤器)相比,大容量CVVH联合定期更换滤器在脓毒症保护方面具有显著优势。第4组67%的动物和第3组33%的动物存活超过60小时(p <.05),而对照组和第2组无动物存活。CVVH改善了最初的血清肿瘤坏死因子-α反应,并预防了脓毒症诱导的体外内毒素低反应性。CVVH显著改善了单核细胞上主要组织相容性复合体II和CD14表达的下调。多形核白细胞氧化爆发和吞噬能力的改善表明CVVH使白细胞功能得以稳定。此外,CVVH显著减少了细菌移位和内毒素血症。

结论

在胆汁酸诱导的胰腺炎猪模型中,血液滤过逆转了脓毒症诱导的免疫麻痹。对人类胰腺炎的影响必须在前瞻性临床方案中得到验证。

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