Терапия глюкокортикоидами при сепсисе и септическом шоке

Два новых метаанализа суммируют влияние глюкокортикоидов на лечение пациентов с сепсисом и септическим шоком.

Оба анализа, как и предыдущие исследования, показали, что применение глюкокортикоидов (как правило, гидрокортизона) приводит к более быстрому выведению пациентов из септического шока. Глюкокортикоиды также, по-видимому, уменьшают продолжительность нахождения пациентов на искусственной вентиляции лёгких и уменьшают длительность интенсивной терапии. Наряду с этим результаты исследований ещё раз напоминают, что применение глюокортикоидов могут приводить к увеличению риска возникновения неблагоприятных побочных эффектов, таких как гипернатриемия, гипергликемия и нервно-мышечная слабость. Эти результаты ещё раз подтверждают необходимость индивидуального подхода к применению глюкокортикоидов при лечении сепсиса и септического шока.

Источники: Intensive Care Med. 2018 Jul;44(7):1003-1016. doi: 10.1007/s00134-018-5197-6. Epub 2018 May 14.

                    Crit Care Med. 2018 Sep;46(9):1411-1420. doi: 10.1097/CCM.0000000000003262.

Corticosteroids in Sepsis: An Updated Systematic Review and Meta-Analysis.

Rochwerg B et al

OBJECTIVE:

This systematic review and meta-analysis addresses the efficacy and safety of corticosteroids in critically ill patients with sepsis.

DATA SOURCES:

We updated a comprehensive search of MEDLINE, EMBASE, CENTRAL, and LILACS, and unpublished sources for randomized controlled trials that compared any corticosteroid to placebo or no corticosteroid in critically ill children and adults with sepsis.

STUDY SELECTION:

Reviewers conducted duplicate screening of citations, data abstraction, and, using a modified Cochrane risk of bias tool, individual study risk of bias assessment.

DATA EXTRACTION:

A parallel guideline committee provided input on the design and interpretation of the systematic review, including the selection of outcomes important to patients. We assessed overall certainty in evidence using Grading of Recommendations Assessment, Development and Evaluation methodology and performed all analyses using random-effect models. For subgroup analyses, we performed metaregression and considered p value less than 0.05 as significant.

DATA SYNTHESIS:

Forty-two randomized controlled trials including 10,194 patients proved eligible. Based on low certainty, corticosteroids may achieve a small reduction or no reduction in the relative risk of dying in the short-term (28-31 d) (relative risk, 0.93; 95% CI, 0.84-1.03; 1.8% absolute risk reduction; 95% CI, 4.1% reduction to 0.8% increase), and possibly achieve a small effect on long-term mortality (60 d to 1 yr) based on moderate certainty (relative risk, 0.94; 95% CI, 0.89-1.00; 2.2% absolute risk reduction; 95% CI, 4.1% reduction to no effect). Corticosteroids probably result in small reductions in length of stay in ICU (mean difference, -0.73 d; 95% CI, -1.78 to 0.31) and hospital (mean difference, -0.73 d; 95% CI, -2.06 to 0.60) (moderate certainty). Corticosteroids result in higher rates of shock reversal at day 7 (relative risk, 1.26; 95% CI, 1.12-1.42) and lower Sequential Organ Failure Assessment scores at day 7 (mean difference, -1.39; 95% CI, -1.88 to -0.89) (high certainty). Corticosteroids likely increase the risk of hypernatremia (relative risk, 1.64; 95% CI, 1.32-2.03) and hyperglycemia (relative risk, 1.16; 95% CI, 1.08-1.24) (moderate certainty), may increase the risk of neuromuscular weakness (relative risk, 1.21; 95% CI, 1.01-1.52) (low certainty), and appear to have no other adverse effects (low or very low certainty). Subgroup analysis did not demonstrate a credible subgroup effect on any of the outcomes of interest (p > 0.05 for all).

CONCLUSIONS:

In critically ill patients with sepsis, corticosteroids possibly result in a small reduction in mortality while also possibly increasing the risk of neuromuscular weakness.

PubMed

Low-dose corticosteroids for adult patients with septic shock: a systematic review with meta-analysis and trial sequential analysis.

Rygård SL et al

PURPOSE:

To assess the effect of low dose corticosteroids on outcomes in adults with septic shock.

METHODS:

We systematically reviewed randomised clinical trials (RCTs) comparing low-dose corticosteroids to placebo in adults with septic shock. Trial selection, data abstraction and risk of bias assessment were performed in duplicate. The primary outcome was short-term mortality. Secondary and tertiary outcomes included longer-term mortality, adverse events, quality of life, and duration of shock, mechanical ventilation and ICU stay.

RESULTS:

There were 22 RCTs, including 7297 participants, providing data on short-term mortality. In two low risk of bias trials, the relative risk (RR) of short-term mortality with corticosteroid versus placebo was 0.98 [95% confidence interval (CI) 0.89-1.08, p = 0.71]. Sensitivity analysis including all trials was similar (RR 0.96; 95% CI 0.91-1.02, p = 0.21) as was analysis of longer-term mortality (RR 0.96; 95% CI 0.90-1.02, p = 0.18). In low risk of bias trials, the risk of experiencing any adverse event was higher with corticosteroids; however, there was substantial heterogeneity (RR 1.66; 95% CI 1.03-2.70, p = 0.04, I2 = 78%). No trials reported quality of life outcomes. Duration of shock [mean difference (MD) -1.52 days; 95% CI -1.71 to -1.32, p < 0.0001], duration of mechanical ventilation (MD -1.38 days; 95% CI -1.96 to -0.80, p < 0.0001), and ICU stay (MD -0.75 days; 95% CI -1.34 to -0.17, p = 0.01) were shorter with corticosteroids versus placebo.

CONCLUSIONS:

In adults with septic shock treated with low dose corticosteroids, short- and longer-term mortality are unaffected, adverse events increase, but duration of shock, mechanical ventilation and ICU stay are reduced. PROSPERO registration no. CRD42017084037.

KEYWORDS:

Corticosteroids; Meta-analysis; Sepsis; Septic shock

PubMed

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