Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock

 

Abstract

Background

Mortality from sepsis and septic shock remains high. Results of trials on intravenous immunoglobulins (IVIG) as adjunctive therapy for sepsis have been conflicting. This is an update of a Cochrane review (2002).

Objectives

To estimate the effects of IVIG on mortality and duration of hospitalization in patients with sepsis or septic shock.

Search methods

We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 4), MEDLINE (1966 to October 2008), and EMBASE (1988 to October 2008). We contacted investigators in the field for unpublished data.

Selection criteria

We included randomized controlled trials comparing IVIG (monoclonal or polyclonal) with placebo or no intervention in patients with bacterial sepsis or septic shock.

Data collection and analysis

Two reviewers independently assessed the studies for inclusion, methodologic quality and data abstraction. We conducted pre-specified subgroup analyses by type of immunoglobulin preparation.

Main results

Forty-two of 84 potentially eligible studies met our inclusion criteria. Pooled analysis of polyclonal and monoclonal IVIG was not done due to clinical heterogeneity. Subgroup analysis of 10 polyclonal IVIG trials in adults (n = 1430) and seven trials on IgM-enriched polyclonal IVIG (n = 528) showed significant reductions in mortality compared to placebo or no intervention (RR 0.81; 95% CI 0.70 to 0.93 and RR 0.66; 95% CI 0.51 to 0.85, respectively). Subgroup analysis of polyclonal IVIG in neonates showed no significant reduction in mortality for standard (RR 0.90; 95% CI 0.46 to 1.76; 4 trials, n = 174) and IgM-enriched polyclonal IVIG (RR 0.57; 95% CI 0.31 to 1.04; 3 trials, n = 164). Sensitivity analysis of trials with low risk of bias showed no reduction in mortality with polyclonal IVIG in adults (RR 0.97; 95% CI 0.81 to 1.15; 5 trials, n = 945) and neonates (RR 0.41; 95% CI 0.16 to 1.08; 3 trials, n = 128). Mortality was not reduced among patients (8 trials, n = 4671) who received anti-endotoxin antibodies (RR 0.99; 95% CI 0.91 to1.06) while anti-cytokines (9 trials, n = 7893) demonstrated a marginal reduction in mortality (RR 0.92; 95% CI 0.86 to 0.97).

Authors' conclusions

Polyclonal IVIG reduced mortality among adults with sepsis but this benefit was not seen in trials with low risk of bias. Among neonates, no reduction in mortality was seen with polyclonal IVIG. Most of the trials were small and the totality of the evidence is insufficient to support a robust conclusion of benefit. Adjunctive therapy with monoclonal IVIGs remains experimental.

 

Plain language summary

Intravenous immunoglobulin for treating patients with severe sepsis and septic shock

Sepsis is the inflammatory response of the body to severe infection, which can be caused by a variety of bacteria. Deaths due to sepsis and septic shock remain high despite giving antibiotics, especially if the performance of people's vital organs such as the lungs, heart and kidney are affected. Several studies have looked into other agents to help the body fight the effects of sepsis. Intravenous immunoglobulin preparations contain antibodies that help the body to neutralize bacterial toxins. There are two types of preparations, polyclonal immunoglobulins contain several antibodies and monoclonal immunoglobulins target a specific antigen. This updated review found 24 trials of polyclonal immunoglobulins, with 17 in adults (1958 participants) and seven in newborn infants (338 participants); 18 trials (a total of 13,413 participants) were of monoclonal antibodies. Both standard and IgM-enriched polyclonal immunoglobulins decreased the number of deaths in adults but not in infants. No reductions in deaths of adults or infants were seen with polyclonal IVIG using high quality trials only. In the monoclonal immunoglobulin trials, anti-endotoxin antibodies showed no benefit while the anti-cytokines showed a very small reduction in deaths among adults with sepsis. The polyclonal immunoglobulin trials were small compared to the trials of monoclonal preparations. The reduction in deaths observed with polyclonal preparations needs to be confirmed in large studies that use high quality methods.

 

摘要

背景

使用靜脈注射的免疫球蛋白(IVIG)治療敗血症及敗血性休克

嚴重敗血症及敗血症休克所產生的死亡是很常見的，許多學者針對抗體是否能有效降低細菌內毒素所產生的死亡率進行研究。

目標

在菌血症或敗血症休克的病人身上給予靜脈注射免疫球蛋白，評估病患的死亡率、細菌失敗率(bacteriological failure rates)及病人住院天數。

搜尋策略

搜尋Cochrane Infectious Diseases Group截至2002年十月登記的病例；及the Cochrane Controlled Trails Register、2002年的 The Cochrane Library issue 3;MEDLINE 1996年至2002年十月; 還有EMBASE 1980至2002年十月登記的病例。並主動聯繫在這個領域擁有資料尚未發表的研究者。

選擇標準

比較細菌性敗血症或敗血性休克病患接受單株性或多株性靜脈注射免疫球蛋白與安慰劑、或不作任何治療的隨機分配實驗。

資料收集與分析

依照選擇標準, 評估試驗的品質及隨機選取其資料後,分出不同種類免疫球蛋白的子群體所做的分析。

主要結論

55個研究中有27個符合入選條件。分析所有種類的靜脈注射免疫球蛋白研究後顯示死亡率有意義地降低(n = 8,856; RR = 0.91; 95%CI 0.86 – 0.96)。接受多株性靜脈注射免疫球蛋白的病患整體死亡率降低了(n = 492; RR = 0.64; 95% CI 0.51 to0.80)。兩個高品質的多株性靜脈注射免疫球蛋白研究顯示, 整體死亡率RR值為0.3,但是信賴區間是寬的。病患接受單株抗體, 例如 antiendotoxins或 anticytokines的研究發現死亡率沒有降低。一些研究計算出次要結果顯示實驗組跟對照組的結果沒有差異, 除接受多株性靜脈注射免疫球蛋白者有意義地降低了跟敗血症相關的死亡率。

作者結論

多株性靜脈注射免疫球蛋白有意義地降低死亡率,是最佳治療敗血症跟敗血性休克的佐劑。然而,所有臨床實驗規模小且整體的證據強度不足以支持其有益性。使用單株性靜脈注射免疫球蛋白的治療效果仍在實驗階段。

翻譯人

本摘要由慈濟醫院鄭偉君翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

仍未有概要