Background

Polyclonal or IgM-enriched immunoglobulins may be beneficial during sepsis as an adjuvant immunomodulatory therapy. We aimed to test whether the infusion of IgM-enriched immunoglobulins improves microvascular perfusion during sepsis.

Methods

Single-centre, randomized, double-blind, placebo-controlled phase II trial including adult patients with a diagnosis of sepsis or septic shock for less than 24 h. Patients received an intravenous infusion of 250 mg/kg (5 mL/kg) per day of IgM-enriched immunoglobulins (Pentaglobin, n = 10) for 72 h or placebo (NaCl 0.9%, n = 9). At baseline and after 24 and 72 h of infusion, the sublingual microcirculation was assessed with Incident Dark Field videomicroscopy. Thenar near-infrared spectroscopy (NIRS) was applied with a vascular occlusion test to assess tissue oxygenation and microvascular reactivity. Levels of interleukin (IL) 1-beta, IL-6, IL-8, IL-10 and tumour necrosis factor alpha were measured in the serum.

Results

The perfused vessel density (PVD) for small vessels (diameter < 20 micron) increased in the Pentaglobin group (from 21.7 ± 4.7 to 25.5 ± 5.1 mm/mm²) and decreased in the placebo group (from 25 ± 5.8 to 20.7 ± 4.1 mm/mm², p for interaction < 0.001, two-way analysis of variance). The absolute between-group difference at 72 h was 4.77 (standard error 2.34), p = 0.140. The microvascular flow index for small vessels increased at 24 h in the Pentaglobin group (from 2.68 [2.38–2.78] to 2.93 [2.82–3], p < 0.01) and decreased at 72 h in the placebo group (from 2.83 [2.60–2.97] to 2.67 [2.48–2.73], p < 0.05). Changes in general parameters, cytokines and NIRS-derived parameters were similar between the two groups, except for IL-6 and IL-10 that significantly decreased at 72 h only in the Pentaglobin group.

Conclusions

A 72-h infusion of IgM-enriched immunoglobulins (Pentaglobin) in patients with sepsis or septic shock may be associated with an increase in sublingual microvascular perfusion. Further studies are needed to confirm our findings.Trial registration NCT02655133, www.ClinicalTrials.gov, date of registration 7th January 2016, https://www.clinicaltrials.gov/ct2/show/NCT02655133.

中文翻译：

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富含IgM的免疫球蛋白（Pentaglobin）可能会改善脓毒症的微循环：一项随机试验。

背景

在脓毒症期间，多克隆或富含IgM的免疫球蛋白可能作为辅助免疫调节疗法是有益的。我们旨在测试输注富含IgM的免疫球蛋白是否可改善败血症期间的微血管灌注。

方法

单中心，随机，双盲，安慰剂对照的II期临床试验，包括诊断为败血症或败血性休克的成年患者，少于24小时。患者每天接受250 mg / kg（5 mL / kg）富含IgM的免疫球蛋白（Pentaglobin，n  = 10）静脉输注72 h或安慰剂（NaCl 0.9％，n  = 9）。在基线以及输注24和72 h后，用突发暗场视频显微镜评估舌下微循环。纳那尔近红外光谱仪（NIRS）进行了血管阻塞试验，以评估组织的氧合作用和微血管反应性。在血清中测量白介素（IL）1-β，IL-6，IL-8，IL-10和肿瘤坏死因子α的水平。

结果

在五肽组中，小血管（直径<20微米）的灌注血管密度（PVD）增加（从21.7±4.7降低到25.5±5.1 mm / mm ²），在安慰剂组降低（从25±5.8降低到20.7±4.1） mm / mm ²，交互作用的p <0.001，双向分析。72小时时的绝对组间差异为4.77（标准误2.34），p  = 0.140。五肽组的小血管微血管流动指数在24小时增加（从2.68 [2.38–2.78]降至2.93 [2.82–3]，p  <0.01），而在安慰剂组在72 h下降（从2.83 [2.60–2.6] 2.97]至2.67 [2.48–2.73]，p <0.05）。两组之间的一般参数，细胞因子和NIRS衍生参数的变化相似，除了IL-6和IL-10仅在Pentaglobin组中在72 h时才显着降低。

结论

败血症或败血性休克患者中输注富含IgM的免疫球蛋白（Pentaglobin）72小时可能与舌下微血管灌注增加有关。需要进一步的研究以确认我们的发现。试用注册NCT02655133，www.ClinicalTrials.gov，注册日期2016年1月7日，https：//www.clinicaltrials.gov/ct2/show/NCT02655133。