Impact and Beneficial Critical Points of Clinical Outcome in Corticosteroid Management of Adult Patients With Sepsis: Meta-Analysis and GRADE Assessment

Abstract

Background: With new randomised pieces of evidence and the latest clinical practice guideline from the BMJ emerging in 2018, an updated analysis of best available evidence on the controversial effects of corticosteroids in sepsis is warranted.Objectives: To comprehensively evaluate whether corticosteroids are beneficial in reducing mortality and what cumulative dosage, daily dosage, and duration of corticosteroid treatment would enable adult patients with sepsis to reach the critical point of benefits.Methods: Ovid MEDLINE, Ovid EMbase, Cochrane Library, and LILACS database were searched until March 22, 2019.Results: Thirty RCTs with 8,836 participants were identified. Long course low-dose corticosteroid therapy could improve 28-day mortality (RR = 0.90, 95% CI = 0.84–0.97; high quality), intensive care unit mortality (RR = 0.87; 95% CI = 0.79–0.95; moderate quality), and in-hospital mortality (RR = 0.88, 95% CI = 0.79–0.997; high quality). However, we found no benefits for 90-day, 180-day, and 1-year mortality. Subgroup results of long course corticosteroid treatment in a population with septic shock and vasopressor-dependent septic shock, corticosteroid regimen with hydrocortisone plus fludrocortisone, corticosteroid dosing strategies including bolus dosing and infusion dosing, the strategies of abrupt discontinuation, timing of randomisation ≤24 h, impact factor of ≥10, and sample size ≥500 were associated with a marginally reduction in 28-day mortality.Conclusions: This meta-analysis found that the long course low-dose and not short course high-dose corticosteroid treatment could marginally improve short-term 28-day mortality with high quality, especially septic shock and vasopressor-dependent septic shock, and it is recommended that long course (about 7 days) low-dose (about 200–300mg per day) hydrocortisone (or equivalent) with cumulative dose (at least about 1,000mg) may be a viable management option for overall patients with sepsis, and it can be also adapted to patient with septic shock alone. Early hydrocortisone plus fludrocortisone administration, via continuous infusion or bolus dosing, is also particularly important for the prognosis. Abrupt discontinuation of corticosteroids, as opposed to the conventional tapered discontinuation, may be considered as a desirable option in 28-day mortality. The safety profile of long course low-dose corticosteroid treatment, including adverse hyperglycaemia and hypernatraemia events, remains a concern, although these events could be easily treated.Clinical Trial Registration: PROSPERO, identifier CRD 42018092849.

Fludrocortisone Plus Hydrocortisone Versus Hydrocortisone Alone as Adjunctive Therapy in Septic Shock: A Retrospective Cohort Study

“…9,10 Long courses (≥4 days) of corticosteroids at low doses (200-300 mg/day) have been shown to improve mortality in this patient population. 25-27 More than half the patients in our study had corticosteroids tapered. A systematic review by Annane and colleagues found a significant reduction in risk of 28-day mortality in those trials where corticosteroids were not tapered (ie, Ger-Inf-05, ADRENAL, and APROCCHSS).…”

The effects of antioxidant supplementation on short-term mortality in sepsis patients

“…The appropriate corticosteroid dosage and duration of treatment are still uncertain [ 92 ]. Even though short-term low-dose corticosteroid therapy may be beneficial [ 93 , 94 ], standardised adrenal function testing was still required to assist reverse septic shock and reduce mortality [ [95] , [96] , [97] ].…”

Aspek Farmakologi dan Indikasi Corticosteroid

“…Pada kondisi stres, mungkin diperlukan dosis hingga 300 mg setiap hari untuk mencegah tanda dan gejala insufisiensi adrenal, termasuk hipoglikemia, hipotensi, dan kolaps kardiovaskular. 39 Titrasi dosis dan optimalisasi terapi kronis mungkin diperlukan untuk mencegah efek samping. Fludrocortisone merupakan bentuk sintetis aldosteron yang dapat ditambahkan untuk meningkatkan kontrol penyakit insufisiensi adrenal, umumnya dengan dosis 0,1 mg setiap hari.…”