Steroids reduced the duration of septic shock and the time spent on life support therapy in intensive care, but did not lead to fewer deaths overall, an international trial conducted in 3,800 patients found.
The results from the largest ever study of septic shock could improve treatment for critically ill patients and save health systems worldwide hundreds of millions of dollars each year. Researchers at The George Institute for Global Health studied whether the use of steroids as an additional treatment to septic shock – a severe life threatening infection – would improve survival.
In the results, they found steroids not only reduced the duration of septic shock, but also the time spent on life support therapy in intensive care. However, the use of steroids did not lead to fewer deaths overall compared to not receiving steroids.
Lead author Professor Bala Venkatesh, of The George Institute for Global Health, said: "Our results show there is still a lot to learn about septic shock which kills up to half of those affected in some parts of the world. There are undoubtedly many other contributors to survival which we don't yet understand.
"But, we have finally shown what part steroids play in the treatment of these patients. If we can reduce the time in spent in intensive care units that not only frees up space for other patients, it saves health systems worldwide a huge amount of money."
Steroids have been used for over 50 years to treat septic shock – life threatening illness that occurs when the body's response to infection leads to low blood pressure that reduces blood flow to vital organs and tissues such as the heart, brain, kidney and liver. Steroids are thought to improve the circulation by counteracting the severe inflammation seen in septic shock. However, there was uncertainty about the optimal dose and duration of steroids and concerns that steroids may result in adverse complications to patients.
In this international trial conducted in 3,800 patients in Australia, New Zealand, the UK, Denmark and Saudi Arabia, researchers showed that while the use of steroids did not reduce death rates, steroids led to a more rapid resolution of shock, were taken off mechanical ventilation earlier, received less blood transfusions and were discharged from intensive care earlier than those patients who did not receive steroids.
The trial will add high-quality evidence about the safe and effective use of steroids for patients with septic shock. Co-author Professor John Myburgh, of The George Institute for Global Health, said: "Anyone can get sepsis, young, old, fit and healthy. It does not discriminate. Those that survive can be left with substantial injuries such as amputated limbs, and post-traumatic stress disorder.
"It is essential that we raise awareness of this disease so people can get treatment more quickly, but we will also need to find better and more effective care for those who go into septic shock."
The study was supported by a grant from the National Health and Medical Research Council of Australia (NHMRC).
Background: Whether hydrocortisone reduces mortality among patients with septic shock is unclear.
Methods: We randomly assigned patients with septic shock who were undergoing mechanical ventilation to receive hydrocortisone (at a dose of 200 mg per day) or placebo for 7 days or until death or discharge from the intensive care unit (ICU), whichever came first. The primary outcome was death from any cause at 90 days.
Results: From March 2013 through April 2017, a total of 3800 patients underwent randomization. Status with respect to the primary outcome was ascertained in 3658 patients (1832 of whom had been assigned to the hydrocortisone group and 1826 to the placebo group). At 90 days, 511 patients (27.9%) in the hydrocortisone group and 526 (28.8%) in the placebo group had died (odds ratio, 0.95; 95% confidence interval [CI], 0.82 to 1.10; P=0.50). The effect of the trial regimen was similar in six prespecified subgroups. Patients who had been assigned to receive hydrocortisone had faster resolution of shock than those assigned to the placebo group (median duration, 3 days [interquartile range, 2 to 5] vs. 4 days [interquartile range, 2 to 9]; hazard ratio, 1.32; 95% CI, 1.23 to 1.41; P<0.001). Patients in the hydrocortisone group had a shorter duration of the initial episode of mechanical ventilation than those in the placebo group (median, 6 days [interquartile range, 3 to 18] vs. 7 days [interquartile range, 3 to 24]; hazard ratio, 1.13; 95% CI, 1.05 to 1.22; P<0.001), but taking into account episodes of recurrence of ventilation, there were no significant differences in the number of days alive and free from mechanical ventilation. Fewer patients in the hydrocortisone group than in the placebo group received a blood transfusion (37.0% vs. 41.7%; odds ratio, 0.82; 95% CI, 0.72 to 0.94; P=0.004). There were no significant between-group differences with respect to mortality at 28 days, the rate of recurrence of shock, the number of days alive and out of the ICU, the number of days alive and out of the hospital, the recurrence of mechanical ventilation, the rate of renal-replacement therapy, and the incidence of new-onset bacteremia or fungemia.
Conclusions: Among patients with septic shock undergoing mechanical ventilation, a continuous infusion of hydrocortisone did not result in lower 90-day mortality than placebo.
Balasubramanian Venkatesh, Simon Finfer, Jeremy Cohen, Dorrilyn Rajbhandari, Yaseen Arabi, Rinaldo Bellomo, Laurent Billot, Maryam Correa, Parisa Glass, Meg Harward, Christopher Joyce, Qiang Li, Colin McArthur, Anders Perner, Andrew Rhodes, Kelly Thompson, Steve Webb, John Myburgh
[link url="https://www.sciencedaily.com/releases/2018/01/180119085945.htm"]George Institute of Global Health material[/link]
[link url="http://www.nejm.org/doi/10.1056/NEJMoa1705835"]New England Journal of Medicine abstract[/link]