ENDOTOXIN CONCENTRATION IN NEUTROPENIC PATIENTS WITH SUSPECTED GRAM-NEGATIVE SEPSIS - CORRELATION WITH CLINICAL OUTCOME AND DETERMINATION OF ANTIENDOTOXIN CORE ANTIBODIES DURING THERAPY WITH POLYCLONAL IMMUNOGLOBULIN-M-ENRICHED IMMUNOGLOBULINS
ENDOTOXIN CONCENTRATION IN NEUTROPENIC PATIENTS WITH SUSPECTED GRAM-NEGATIVE SEPSIS - CORRELATION WITH CLINICAL OUTCOME AND DETERMINATION OF ANTIENDOTOXIN CORE ANTIBODIES DURING THERAPY WITH POLYCLONAL IMMUNOGLOBULIN-M-ENRICHED IMMUNOGLOBULINS
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DOI：
10.1128/aac.36.10.2139
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发表时间：
1992-10-01
影响因子：
4.9
通讯作者：
HIDDEMANN, W
中科院分区：
文献类型：
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作者：
BEHRE, G;SCHEDEL, I;HIDDEMANN, W
我们对血液系统恶性肿瘤和疑似革兰氏阴性脓毒症的严重中性粒细胞减少症患者进行了一项研究，以评估在使用人类多克隆免疫球蛋白M(IgM)强化免疫球蛋白制剂(德国德雷伊奇的Biotest)进行治疗干预之前和期间血浆内毒素浓度的临床意义。21例急性白血病或非霍奇金淋巴瘤患者出现革兰氏阴性脓毒症的临床体征，在常规抗生素治疗的基础上，每隔6h接受一次免疫球蛋白强化治疗，共3天(总剂量1.3升，其中包括7.8g、7.8g、49.4g)。分别于每次免疫球蛋白输注前和注射后25d，用改良的显色法、半定量酶联免疫吸附试验检测血浆内毒素、抗A型类脂蛋白和脂多糖抗体的IgM和Ig G浓度。17名患者内毒素呈阳性；其中5名患者的微生物检查结果证实为革兰氏阴性感染。在治疗前，内毒素血症与发热的发生显著相关，17例患者中有8例在个体感染过程中内毒素浓度与体温之间存在定量相关性。在有感染性休克症状的患者中，内毒素阳性脓毒症的总死亡率为41%(7/17)，为7%(7/11)。在研究的第一天，死亡者的血浆内毒素最大浓度显著高于存活者(中位数分别为126和34pg/ml；P<；0.05)，并且在整个脓毒症发作期间(中位数分别为126和61pg/ml；P<；0.05)。在幸存者中，免疫球蛋白治疗导致血浆内毒素水平在最初的18小时内显著下降，从治疗前的中位数28pg/ml降至8pg/ml(P<；0.05)。在7例死于不可控感染的患者中，未观察到治疗对血浆内毒素水平的影响。免疫球蛋白治疗后，抗脂蛋白A和Re-内毒素的IgM和Ig G抗体显著升高，且抗脂蛋白A和Re-内毒素的抗体之间存在显著的相关性。这些数据强烈提示血浆内毒素水平的预后意义，以及多克隆免疫球蛋白制剂治疗的潜在效果。需要进一步的研究来证实这些发现，并通过前瞻性的安慰剂对照临床试验来评估其对临床病程的影响。
We carried out a study in patients with severe neutropenia from hematologic malignancy and suspected gram-negative sepsis to evaluate the clinical significance of endotoxin concentrations in plasma before and during a therapeutic intervention with a human polyclonal immunoglobulin M (IgM)-enriched immunoglobulin preparation (Pentaglobin; Biotest, Dreieich, Germany). Twenty-one patients with acute leukemia or non-Hodgkin's lymphoma entered the study upon the development of clinical signs of gram-negative sepsis and received the IgM-enriched immunoglobulin preparation every 6 h for 3 days (total dose, 1.3 liter with 7.8 g of IgM, 7.8 g of IgA, and 49.4 g of IgG), in addition to standardized antibiotic treatment. Concentrations of endotoxin and IgM and IgG antibodies against lipid A and Re lipopolysaccharide (LPS) in plasma were determined by a modified chromogenic Limulus amebocyte lysate test and semiquantitative enzyme linked immunosorbent assay, respectively, before each immunoglobulin infusion and during the following 25 days. Seventeen patients were endotoxin positive; in five of these patients, gram-negative infection was confirmed by microbiologic findings. Prior to therapy, endotoxemia correlated significantly with the occurrence of fever, and a quantitative correlation between the endotoxin concentration and body temperature was found during the individual course of infection in 8 of the 17 patients. Overall mortality from endotoxin-positive sepsis was 41% (7 of 17) and 64% (7 of 11) in patients with symptoms of septic shock. Nonsurvivors had significantly higher maximum concentrations of endotoxin in plasma compared with those of survivors at the first study day (median of 126 versus 34 pg/ml; P < 0.05) and during the whole septic episode (median of 126 versus 61 pg/ml; P < 0.05). In survivors, immunoglobulin therapy resulted in a significant decrease in endotoxin levels in plasma within the initial 18-h treatment period, from a pretreatment median value of 28 pg/ml to a value of 8 pg/ml (P < 0.05). In the seven patients who died from uncontrollable infection, no effect of therapy on endotoxin levels in plasma was observed. IgM and IgG antibodies against lipid A and Re LPS increased significantly under immunoglobulin treatment, with significant correlations between antibodies against lipid A and Re LPS. These data strongly suggest a prognostic significance of the endotoxin levels in plasma and a potential effect of treatment with a polyclonal IgM-enriched immunoglobulin preparation. Further studies are needed to substantiate these findings and to assess the impact on the clinical course by way of a prospective placebo-controlled clinical trial.