Key messages
• Compared to placebo or usual care, corticosteroids probably reduce the risk of death at 28 days and of in-hospital death, and may have little or no effect on the risk of dying beyond three months.
• We are uncertain about the effects of continuous intravenous infusion of corticosteroids compared with intermittent intravenous bolus (rapid injection) administration.
• Future studies should measure the benefits and harms of corticosteroids for the treatment of specific populations, including children, patients with sepsis without shock or with a mild form of septic shock, patients with acute respiratory distress syndrome (ARDS) and patients with different types of infections. Defining the optimal methods for corticosteroid administration, including the types of molecule - with or without producing sodium and fluid retention and potassium excretion (mineralocorticoid activity), timing of initiation, dose and duration, continuous infusion or intermittent intravenous boluses, and ending of treatment - with or without gradually decreasing the dose to zero, also requires additional studies. Future studies should measure the longer-term effects, i.e. longer than one year, on survival and complications of sepsis.
What is sepsis?
Sepsis is present when an infection is complicated by organ failure. People develop rapid breathing, hypotension (low blood pressure) and mental confusion. Sepsis can interfere with the effectiveness of the body’s corticosteroids, which control how your body recognises and defends itself against bacteria, viruses and substances that appear foreign and harmful.
What are corticosteroids (medicine)?
Corticosteroids are medicines used to stop excessive inflammation. However, these medicines may cause unwanted harms, such as increased blood sugar or salt levels, infections, bleeding in the stomach, agitation or delirium, and weakness of the limbs. Corticosteroids have been given for decades to people with infection resulting from various causes.
What did we want to find out?
We wanted to find out:
• the benefits of using corticosteroids in children and adults with sepsis; and
• the best ways to administer this treatment (including the best people to give it to).
We also wanted to know if corticosteroids can cause any unwanted effects.
What did we do?
We searched for studies that compared:
• corticosteroids administered intravenously against a 'dummy' treatment, or sham treatment, which does not contain any medicine but looks or tastes identical to corticosteroids, or usual care; or
• continuous infusion against intermittent rapid intravenous injections (boluses) of corticosteroids administration.
We compared and summarised their results, and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
This review includes 87 trials (24,336 participants). The biggest study was of 3800 people and the smallest study was of 21 people. Eighty-three trials compared corticosteroids to no corticosteroids (placebo or usual care in 59 and 24 trials, respectively). Four trials also compared continuous administration versus rapid intravenous injection (i.e. bolus) of corticosteroids given at fixed intervals of six or eight hours. Thirty-three trials were conducted in Europe, 15 in North America, 22 in Asia, six in the Middle East, six in Africa and three in Latin America; four were multinational trials.
Three trials were funded by a drug company, 27 by public organisations or through charitable funding and six by both a drug company and public organisations or charitable funding; 25 did not declare the source of funding.
Compared to placebo or usual care, corticosteroids probably reduce the risk of death at 28 days by 10% (72 trials; 22,915 participants), with consistent treatment effects between children and adults. There may be little or no effect of corticosteroids on the risk of dying over the long term (longer than three months), but these results are less certain. Corticosteroids probably reduce the risk of dying in hospital. Corticosteroids may result in a reduction in the length of stay in the intensive care unit (ICU) and in hospital. They may not increase the risk of superinfection (second infection). The evidence is very uncertain about the effect of corticosteroids on the risk of muscle weakness.
We are uncertain about the effects of continuous intravenous infusion of corticosteroids compared with intermittent intravenous bolus (rapid injection) administration. Four studies reported data for this comparison, and the certainty of evidence for all outcomes was very low.
What are the limitations of the evidence?
• Corticosteroids versus placebo or usual care
We have moderate confidence in our findings that corticosteroids reduced 28-day mortality. We found some differences amongst the study populations, the types of corticosteroids and how they were given, and the use of additional medicines.
• Continuous infusion versus bolus administration of corticosteroids
We have very little confidence in our findings about the absence of a difference in 28-day mortality between the administration of corticosteroids continuously and repeated rapid intravenous injections. We found only four studies that enrolled very few patients.
How up-to-date is this evidence?
The evidence provided in this review is current to December 2023.