Objective: to assess and compare early corticosteroid treatment at the onset of septic shock (in the first stage) with conventional administration of corticosteroids in the third stage of treatment.
Design: randomised clinical trial (RCT).
Setting: tertiary level university hospital in Alexandria (Egypt).
Study sample: the study included 96 patients aged 1 month to 4 years admitted to the intensive care unit (ICU) with a diagnosis of septic shock based on international criteria. Patients who were immunosuppressed, patients with adrenal diseases or diseases affecting the pituitary function and patients treated with long-term corticosteroids within the past 6 months or short-term corticosteroids within the past 4 weeks were excluded.
Intervention: patients were divided in four groups: group A, with 32 patients, received conventional treatment; group B, with 32 patients, received the same treatment as group A with the addition of the adrenocorticotropic hormone (ACTH) stimulation test, considered positive if there was an increase in cortisol of more than < 9 µg over the baseline level; group C, with 32 patients, received an intravenous stress dose of hydrocortisone (50 mg/m2/24 h) with continuous infusion for 5 days (intervention group [IG]); and group D, consisting of patients from group A or B that required corticosteroids in the third stage of treatment (36 patients) (control group [CG]).
The patients were randomized by “block randomization” with allocation concealment. The physicians, nurses, data collectors and statistician were blinded to the use of early corticosteroid therapy.
Outcome measures: the outcome measures were the Pediatric Index of Mortality score (PIM); the Pediatric Logistic Organ Dysfunction score (PELOD); shock reversal time in days (maintenance of systolic blood pressure at or above the 5th percentile in infants aged less than 1 year and of 70 mmHg or greater + (2 × age in years) in children aged 1 to 10 years without vasopressor support for 24 hours or more); length of ICU stay, complications; and fate (discharge or death).
Main results: there were significant differences between groups A, B and C in the baseline PIM and PELOD scores and reversal of shock time (p values of.041,.035 and.046, respectively), while the groups had similar demographic and clinical characteristics. The basal serum ACTH level was normal, and serum cortisol was elevated, with no differences between groups. The authors did not find a statistically significant association between nonresponse to adrenal stimulation and the development of complications, the outcome, and the length of stay (p- values of.131,.057 and.959, respectively).
The comparison of the IG (early corticosteroid treatment) and CG (corticosteroid therapy in the third stage of treatment, adhering to conventional protocol) showed that while the PIM and PELOD scores at day 1 were worse in the IG (p-values of.009 and.044), there was a significant difference in favour of the IG on day 3, with a shorter shock reversal time (2.5 ± 0.9 days versus 5.8 ± 1.8; P =.001) and an improved better PELOD score (reduced from 38 ± 11.3 to 16.2 ± 21.5; P =.001). There was no difference in the cumulative hazard of mortality based on length of stay (calculated by means of a Kaplan-Meier survival curves) between groups A, b and C.
Conclusion: early use of corticosteroids in patients with septic shock may shorten shock reversal time without increasing mortality or the incidence of superinfection. Mortality is disappointing as a primary outcome, while shock reversal time is a more plausible endpoint that is also clinically relevant.
Conflicts of interest: none disclosed.
Funding source: none.