сепсис и иммуноглобулины

[mountainbeaver]

почему в протоколе SURVIVING SEPSIS CAMPAIGN 2008 упоминается многое (и кортикостероиды и активированный протеин С), но не затронут вопрос об иммуноглобулинах.
Хотя исследования на эту тему есть
Может я просто невнимательно прочитал протокол?
[Ссылки доступны только зарегистрированным пользователям ]
[Ссылки доступны только зарегистрированным пользователям ]

[cactus1972]

Сообщение от mountainbeaver

почему в протоколе SURVIVING SEPSIS CAMPAIGN 2008 упоминается многое (и кортикостероиды и активированный протеин С), но не затронут вопрос об иммуноглобулинах.
Хотя исследования на эту тему есть
Может я просто невнимательно прочитал протокол?

.

Невнимательно читали Исследование использования поликлональных иммуноглобулинов у новорожденных показало существенное снижение летальности.

We suggest that immunoglobulin may be considered in
children with severe sepsis (Grade 2C). Administration of polyclonal intravenous immunoglobulin has been reported to reduce mortality rate and is a promising adjuvant in the treatment of sepsis and septic shock in
neonates. A recent randomized controlled study of polyclonal immunoglobulin in pediatric sepsis syndrome patients (n = 100), showed a significant reduction in mortality, LOS, and less progress to complications, especially
DIC .

[Vlad34]

[Ссылки доступны только зарегистрированным пользователям ]

A Grade 2C recommendation is a very weak recommendation; other alternatives may be equally reasonable.

[thorn]

Сообщение от mountainbeaver

почему в протоколе SURVIVING SEPSIS CAMPAIGN 2008 упоминается многое (и кортикостероиды и активированный протеин С), но не затронут вопрос об иммуноглобулинах.

И это очень хорошо - меньше поводов спекулировать о назначении дорогостоящих препаратов...
Исследования есть, но результаты их, мягко говоря, неоднозначны. Для рекомендаций этого недостаточно.
Вы приводите часто цитируемый у нас кокрановский мета-анализ филлипинских авторов 2002 года, который больше не обновлялся. Существуют более поздние и качественные работы. Различные результаты - но не выводы - объясняются тем, что в мета-анализ кто-то включает исследования по новорожденным, кто-то - нет, а также кто как трактуе высокое качество исследований. В любом случае, для того чтобы рекомендовать столь дорогостоящие препараты, это недостаточно. Нужны большие качественные клинические исследования.
ЗЫ: Это не относится к таким отдельно рассматриваемым состояниям как gram-positive toxic shock syndromes.
Вот вроде бы полный перечень мета-анализов по проблеме. Оцените выводы.

Cochrane Database Syst Rev. 2002;(1):CD001090.
Intravenous immunoglobulin for treating sepsis and septic shock.
Alejandria MM, Lansang MA, Dans LF, Mantaring JB.
Source
Clinical Epidemiology Unit, University of the Philippines Manila, College of Medicine, 547 P. Gil St., Ermita, Manila, Philippines, 1000. [Ссылки доступны только зарегистрированным пользователям ]
Abstract
BACKGROUND: Death from severe sepsis and septic shock is common, and researchers have explored whether antibodies to the endotoxins in some bacteria reduces mortality.
OBJECTIVES: To estimate the effects of intravenous immunoglobulin (IVIG) in patients with bacterial sepsis or septic shock on mortality, bacteriological failure rates, and duration of stay in hospital.
SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized register up to November 2001; the Cochrane Controlled Trials Register, The Cochrane Library issue 4, 2001; MEDLINE 1966 to November 2001; and EMBASE 1988 to September 2001. We contacted investigators active in the field for unpublished data.
SELECTION CRITERIA: Randomised trials comparing intravenous immunoglobulin (monoclonal or polyclonal) with placebo or no intervention, in patients with bacterial sepsis or septic shock.
DATA COLLECTION AND ANALYSIS: Inclusion criteria, trial quality assessment, and data abstraction were done in duplicate. We conducted pre-specified subgroup analyses by type of immunoglobulin preparation.
MAIN RESULTS: Twenty-seven out of 55 studies met our inclusion criteria. Pooled analysis of all types of IVIG preparations revealed a significant trend toward reduction of mortality (n= 8,856; RR=0.91; 95%CI 0.86-0.96). Overall mortality was reduced in patients who received polyclonal IVIG (n=492; RR=0.64; 95% CI 0.51 to 0.80). For the two high-quality trials on polyclonal IVIG, the RR for overall mortality was 0.30, but the confidence interval was wide (95% CI 0.09 to 0.99, n=91). Mortality was not reduced among patients who received monoclonal antibodies such as anti-endotoxins (n=2,826 in 5 good-quality studies; RR=0.97; 95% CI 0.88 to 1.07) or anti-cytokines (n=4,318; RR=0.93; 95% CI 0.86 to 1.01). A few studies measured secondary outcomes (deaths from sepsis or length of hospitalisation) but no differences in the intervention and control groups were identified except among those who received polyclonal IVIG, where sepsis-related mortality was significantly reduced (n=161; RR=0.35; 95% CI 0.18 to 0.69).
REVIEWER'S CONCLUSIONS: Polyclonal IVIG significantly reduced mortality and and is a promising adjuvant in the treatment of sepsis and septic shock. However, all 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.

Clin Infect Dis. 2004 Jul 1;39(1):38-46. Epub 2004 Jun 1.
Polyclonal immunoglobulin for treatment of bacterial sepsis: a systematic review.
Pildal J, Gøtzsche PC.
Source
The Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark.
Abstract
Randomized trials of adjunctive treatment of bacterial sepsis with polyclonal immunoglobulin show conflicting results. We performed a systematic review and a meta-analysis of the results of randomized trials that compared reductions in mortality rates in patient groups treated with polyclonal immunoglobulin versus either placebo or no treatment in addition to conventional treatment. High-quality trials had adequate concealment of allocation, were double-blinded and placebo-controlled, and made data available for intention-to-treat analyses. Twenty trials were included. Meta-analysis of all trials showed a relative risk of death with immunoglobulin treatment of 0.77 (95% confidence interval [CI], 0.68-0.88). High-quality trials (involving a total of 763 patients, 255 of whom died) showed a relative risk of 1.02 (95% CI, 0.84-1.24), whereas other trials (involving a total of 948 patients, 292 of whom died) showed a relative risk of 0.61 (95% CI, 0.50-0.73). Because high-quality trials failed to demonstrate a reduction in mortality, polyclonal immunoglobulin should not be used for treatment of sepsis except in randomized clinical trials.

Crit Care Med. 2007 Dec;35(12):2686-92.
Polyclonal intravenous immunoglobulin for the treatment of severe sepsis and septic shock in critically ill adults: a systematic review and meta-analysis.
Laupland KB, Kirkpatrick AW, Delaney A.
Source Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada.
Abstract OBJECTIVES: To systematically review the literature to assess whether adjunctive therapy with polyclonal intravenous immunoglobulin (ivIg) reduces mortality among critically ill adults with severe sepsis and septic shock. DATA SOURCE: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases; the meta-register of controlled trials; and the Medical Editors Trial Amnesty register.
STUDY SELECTION: Prospective randomized clinical trials (RCTs) evaluating ivIg treatment in critically ill adults with severe sepsis or septic shock were included. Two reviewers conducted assessment of suitability for inclusion.
DATA EXTRACTION: Two authors independently determined the validity of included studies and extracted data.
DATA SYNTHESIS: The effect of ivIg on all-cause mortality was quantified using a fixed-effect meta-analysis.
RESULTS: Fourteen RCTs published between 1988 and 2006 were included. Most were small, used relatively low doses of ivIg, and included predominantly surgical patients with Gram-negative infections. There was a significant reduction in mortality associated with use of ivIg treatment with a pooled odds ratio of 0.66 (95% confidence interval 0.53-0.83; p < .0005). In general, a greater treatment effect was seen among studies of lower methodological quality, studies using higher doses of ivIg, and studies that did not use albumin as a control. There was evidence of between-study heterogeneity (chi-square p = .009), and this was at least moderate as measured by the I2 value (I2 = 53.8%). When only high-quality studies were pooled, the odds ratio for mortality was 0.96 (95% confidence interval 0.71-1.3; p = .78).
CONCLUSIONS: This meta-analysis demonstrates an overall reduction in mortality with the use of ivIg for the adjunctive treatment of severe sepsis and septic shock in adults, although significant heterogeneity exists among the included trials and this result was not confirmed when only high-quality studies were analyzed. These data warrant a well-designed, adequately powered, and transparently reported clinical trial.

[thorn]

Окончание:

Ann Intern Med. 2007 Feb 6;146(3):193-203.
Meta-analysis: intravenous immunoglobulin in critically ill adult patients with sepsis.
Turgeon AF, Hutton B, Fergusson DA, McIntyre L, Tinmouth AA, Cameron DW, Hébert PC.
Source
Center for Transfusion and Critical Care Research, Ottawa Health Research Institute, the University of Ottawa and the Canadian Blood Service, Ottawa, Ontario, Cananda. [Ссылки доступны только зарегистрированным пользователям ]
Abstract
BACKGROUND:
Intravenous immunoglobulin therapy has been proposed as an adjuvant treatment for sepsis. Yet, its benefit remains unclear, and its use is not currently recommended.
PURPOSE: To evaluate the effect of polyclonal intravenous immunoglobulin therapy on death in critically ill adult patients with sepsis.
DATA SOURCES: MEDLINE (1966 to May 2006) and the Cochrane Central Register of Controlled Trials (May 2006 edition).
STUDY SELECTION: All randomized, controlled trials of critically ill adult patients with sepsis, severe sepsis, or septic shock who received polyclonal intravenous immunoglobulin therapy or placebo or no intervention were selected. No restrictions were made for study language or type of publication. Data extraction: Data were independently extracted by 2 investigators using a standardized form.
DATA SYNTHESIS:
The literature search identified 4096 articles, of which 33 were deemed to be potentially eligible. Twenty trials (n = 2621) met eligibility criteria and were included in the analysis. Polyclonal intravenous immunoglobulin therapy was associated with an overall survival benefit (risk ratio, 0.74 [95% CI, 0.62 to 0.89]) compared with placebo or no intervention. In sensitivity analyses, documented survival improved when the analysis was limited to published, peer-reviewed trials (risk ratio, 0.72 [CI, 0.58 to 0.89]) (17 trials [n = 1865]) and blinded trials (risk ratio, 0.61 [CI, 0.40 to 0.93) (7 trials [n = 896]). Severe sepsis or septic shock (risk ratio, 0.64 [CI, 0.52 to 0.79]) (11 trials [n = 689]), receiving a total dose regimen of 1 gram or more per kilogram of body weight (risk ratio, 0.61 [CI, 0.40 to 0.94]) (7 trials [n = 560]), and receiving therapy for longer than 2 days (risk ratio, 0.66 [CI, 0.53 to 0.82]) (17 trials [n = 1847]) were strongly associated with this survival benefit.
LIMITATIONS: Most trials were published before new developments modifying the care and outcome of critically ill patients with sepsis including early goal-directed therapy and activated protein C treatment, were introduced.
CONCLUSIONS: A survival benefit was observed for patients with sepsis who received polyclonal intravenous immunoglobulin therapy compared with those who received placebo or no intervention. A large, randomized, controlled trial of polyclonal intravenous immunoglobulin therapy should be performed on the basis of the methodological limitations of the current literature, the potential benefit from this therapy in more severely ill patients, and the potential effect of dosage and duration of this therapy.

Crit Care Med. 2007 Dec;35(12):2677-85.
Use of polyclonal immunoglobulins as adjunctive therapy for sepsis or septic shock.
Kreymann KG, de Heer G, Nierhaus A, Kluge S.
Source
Department of Intensive Care, University Medical Centre, Hamburg-Eppendorf, Germany. [Ссылки доступны только зарегистрированным пользователям ]
Abstract
OBJECTIVE: There is ongoing debate about the efficacy of polyvalent immunoglobulins as adjunctive therapy for sepsis or septic shock. Two meta-analyses by the Cochrane collaboration calculated a significant reduction in mortality. However, data of the largest study were missing in one, and a subset of four high-quality studies failed to show an effect in the other. To broaden the database, we performed a meta-analysis of all randomized controlled studies published so far.
DATA SOURCE:
MEDLINE, EMBASE, Cochrane Library of randomized trials, and personal files.
STUDY SELECTION: Meta-analysis of all published randomized controlled studies published on polyvalent immunoglobulins (Ig) for treatment of sepsis or septic shock in adults, children, or neonates.
DATA EXTRACTION: Twenty-seven trials with a total of 2,202 patients fulfilled the inclusion criteria.
DATA SYNTHESIS: As the immunologic state of neonates is different than that of adults or older children, data were evaluated separately for each group. Fifteen trials on 1,492 adults could be included. The pooled effect on mortality was a relative risk of death (RR) of 0.79 (95% confidence interval [CI] 0.69-0.90, p <or= .0003). There was a strong trend in favor of an immunoglobulin preparation enriched with IgA and IgM (IgGAM) (RR = 0.66, 95% CI 0.51-0.84, p <or= .0009) compared with preparations containing only IgG (RR = 0.85, 95% CI 0.73-0.99, p <or= .04). In 12 trials on 710 neonates, the pooled effect on mortality was 0.56 (95% CI 0.42-0.74, p <or= .0001). There was also a positive although less pronounced trend favoring the effect of IgGAM (RR = 0.50, 95% CI 0.34-0.73, p <or= .0003) compared with IgG (RR = 0.63, 95% CI 0.42-0.96, p <or= .03). A sensitivity analysis selecting eight trials in adults and ten in neonates of highest methodological quality confirmed these results.
CONCLUSIONS: Polyvalent immunoglobulins exert a significant effect on mortality in sepsis and septic shock, with a trend in favor of IgGAM.

[mountainbeaver]

Сообщение от thorn

И это очень хорошо - меньше поводов спекулировать о назначении дорогостоящих препаратов...

тем не менее зигрис активно проталкивается
совершенно не собирался пропагандировать здесь иммуноглобулины при сепсисе.

[thorn]

Сообщение от mountainbeaver

тем не менее зигрис активно проталкивается

C зигрисом все-таки несколько иная ситуация... Как-то в последние несколько лет проталкивают его совсем вяло...стоимость и сомнения в эффективности/безопасности делают свое дело. IVIG кажутся более безопасными и для отечественного "шаманского" сознания более приемлемы.

[mountainbeaver]

а предложения лечения anti-TNF после ramses и monarcs более не повторялись?

[cactus1972]

Можно полюбопытствовать, чем вызван Ваш интерес к применению дорогостоящих препаратов, нечасто используемых в рутинной клинической практике? Любопытство? Или "науку делаете"?

[mountainbeaver]

Сообщение от cactus1972

Любопытство? Или "науку делаете"?

надо быть готовым к предложениям покапать абы чего от доброжелателей.

[cactus1972]

Из последних публикаций об ИГ при сепсисе (правда, речь идет о новорожденных)

[Ссылки доступны только зарегистрированным пользователям ]

At 113 hospitals in nine countries, we enrolled 3493 infants receiving antibiotics for suspected or proven serious infection and randomly assigned them to receive two infusions of either polyvalent IgG immune globulin (at a dose of 500 mg per kilogram of body weight) or matching placebo 48 hours apart. The primary outcome was death or major disability at the age of 2 years.

There was no significant between-group difference in the rates of the primary outcome, which occurred in 686 of 1759 infants (39.0%) who received intravenous immune globulin and in 677 of 1734 infants (39.0%) who received placebo (relative risk, 1.00; 95% confidence interval, 0.92 to 1.08). Similarly, there were no significant differences in the rates of secondary outcomes, including the incidence of subsequent sepsis episodes. In follow-up of 2-year-old infants, there were no significant differences in the rates of major or nonmajor disability or of adverse events.

Therapy with intravenous immune globulin had no effect on the outcomes of suspected or proven neonatal sepsis.

[Maximgamburger]

Постараюсь без рекламы)) Несколько (2011г.) пациентов в стадии септикотоксемии ожоговой болезни получли адекватные дозы ИГ, находясь в тяжелом состоянии - не с локальными ожогамии в третьей стадии, хотел сказать. Получены - преимущественно - хорошие результаты, главным критерием была лучшая выживаемость этих пациентов. Пациентов,не получавших ИГ в таком же состоянии для сравнения, к сожалению, гораздо больше, и сравнение не в их пользу.

[Vlad34]

Сообщение от Maximgamburger

Постараюсь без рекламы))

Постарайтесь перечитать Ваш текст еще раз непредвзято. И сравните: "Мы вам толсто намекаем, что те, кто не пользовался нашим Патентованным Отращивателем Волос остались лысыми. И их, к сожалению, гораздо больше". Телевизором повеяло. Не фактами, принимаемыми к рассмотрению в медицине.

[Maximgamburger]

Сообщение от Vlad34

Постарайтесь перечитать Ваш текст еще раз непредвзято. И сравните: "Мы вам толсто намекаем, что те, кто не пользовался нашим Патентованным Отращивателем Волос остались лысыми. И их, к сожалению, гораздо больше". Телевизором повеяло. Не фактами, принимаемыми к рассмотрению в медицине.

Спасибо за тактичный и верный коммент - Просто сложилось впечатление, что тема как бы подталкивает к принятию отрицательного отношения к ИГ или "ждем мнения от .... что можно". А получается - на практике, что не слишком это уж большое зло, хоть и не билет на выписку))