Research Reports - Effects of glucocorticoids on traumatic brain injury related critical illness-related corticosteroid insufficiency

Chin Med J (Engl). 2013 Oct;126(19):3754-61

Zhao ZL, Chen X, Zhu H, Zhang BL, Chai Y, Li XY, Dong JF, Zhang JN

BACKGROUND: Traumatic brain injury (TBI) is a heterogeneous condition that can
lead to critical LLLness-related corticosteroid insufficiency (CIRCI) causing a
high mortality and morbidity. Glucocorticoids were widely used in the clinical
management of TBI, but their benefit has been challenged in some studies and
their efficacy, especially for treating CIRCI in TBI patients, remains unclear.
METHODS: We conducted a meta-analysis of published data to determine if the
controversy is related to clinical dosing and timing of glucocorticoids (GCs)
application. We analyzed published reports in four databases (MEDLINE, EMBASE,
the Cochrane Controlled Trials Register, and CBMdisc). The published data were
stratified into not only low- and high-dose GCs group but also short- and
long-term GCs group to compare their effectiveness in improving TBI outcomes.
RESULTS: We totally identified 16 reports. For low-dose patients, the pooled
relative risks (RRs) for two clinical outcomes of death or a combination of death
and severe disability were 0.95 (95% confidence interval (CI): 0.80 to 1.13) and
0.95 (95% CI: 0.83 to 1.09), respectively. The risks for infection and
gastrointestinal bleeding were 0.85 (95% CI: 0.50 to 1.45) and 0.64 (95% CI: 0.15
to 2.70), respectively. For high-dose group, the pooled RR of death is 1.14 (95%
CI: 1.06 to 1.21). The pooled RRs for infection and gastrointestinal bleeding for
the high-dose patients were 1.04 (95% CI: 0.93 to 1.15) and 1.26 (95% CI: 0.92 to
1.75), respectively. For long-term use group, the pooled RRs for two clinical
outcomes of death or a combination of death and severe disability were 0.98 (95%
CI: 0.87 to 1.12) and 1.00 (95% CI: 0.90 to 1.11), respectively. The risks for
infection and gastrointestinal bleeding were 0.88 (95% CI: 0.71 to 1.11) and 0.96
(95% CI: 0.35 to 2.66), respectively. For short-term use group, the pooled RR of
death is 1.15 (95% CI: 1.07 to 1.23), and importantly the effects on infections
were beneficial in terms of TBI patients suffering from CIRCI.
CONCLUSIONS: This meta-analysis suggests an increased risk of death for TBI
patients on a high dose and short term of glucocorticoids compared with those on
a low dose and long term, for whom a trend towards clinical improvement is
evident. In addition, stress-does of GCs further decrease the pneumonia incidence
in TBI patients suffering from CIRCI. A large-scale multicenter randomized
controlled trial is warranted for testing (1) the efficacy of stress-dose GCs
treatment in the sub-acute phase of TBI (4-21 days after initial trauma), when
CIRCI is most likely to occur; (2) the hypothesis that stress-dose GCs could
boost patients' stress function and ensure survival.

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