Physiological-dose steroid therapy in sepsis [ISRCTN36253388]

Yıldız, Orhan; Doğanay, Mehmet; Aygen, Bilgehan; Güven, Muhammed; Keleştimur, Fahrettin; Tutuş, Ahmet

doi:10.1186/cc1498

Cited by 147 publications

(37 citation statements)

References 43 publications

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“…2). Consistent with our previous analysis, heterogeneity decreased when the 21 trials were partitioned into studies published before 1989 [24,25,27,30–35] and published after 1997 [8,17–23,26,28,29,36]. As the group of trials published before 1989 was identical to our previous analysis, they were analysed in a similar fashion, with subsequent exclusion of a single outlier study from subsequent analyses (Fig.…”

Section: Resultssupporting

confidence: 78%

“…1) [17–23]. Characteristics of the 21 trials included in this analysis are depicted in Table 1 [8,17–36]. All included studies were prospective randomized trials that involved similar co-interventions in each study group, with the exception of the steroid regimen being investigated.…”

Section: Resultsmentioning

confidence: 99%

“…4) [8,20,22,26,36]. Four of the studies defined a non-responder according to a change in cortisol level of <9 μ g/dL from baseline [8,20,22,36]; the fifth study defined a non-responder according to a change in cortisol level of <6 μ g/dL from baseline [26]. The treatment effects of steroids on mortality, based on response to ACTH stimulation testing, were similar (p 0.86), and consistent within each subgroup and overall (non-responder, I 2 = 0%; responder, I 2 = 14%; combined, I 2 = 0%).…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

The effects of steroids during sepsis depend on dose and severity of illness: an updated meta-analysis

Minneci

Deans

Eichacker

et al. 2009

Clinical Microbiology and Infection

109

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A previous meta-analysis determined that the effects of steroids during sepsis were dose-dependent; since then, additional trials have been published. The current analysis updates our previous analysis examining the effects of steroids during sepsis. A literature search from 2004 to 2008 identified seven randomized controlled trials in adult patients; these were added to 14 previously identified trials. The effects of steroids on mortality were highly variable among the 21 trials (p <0.001, I2 = 60%). In trials published before 1989, which involved short courses of high-dose steroids, steroids increased mortality (n = 8, I2 = 14%, OR of death 1.39 (95% CI 1.04–1.86), p 0.03). In trials published after 1997, which involved longer courses of lower-dose steroids, steroids consistently improved shock reversal (n = 7, I2 = 0%, OR of shock reversal 1.66 [95% CI 1.25–2.20), p <0.001), but demonstrated a more heterogeneous beneficial effect on mortality (n = 12, I2 = 25%, OR of death 0.64 (95% CI 0.45–0.93), p 0.02). An inverse linear relationship between severity of illness and the effects of steroids on mortality was identified across all trials (p 0.03) and within the subgroup of trials published after 1997 (p 0.03); steroids were harmful in less severely ill patient populations and beneficial in more severely ill patient populations. There was no effect of response to adrenocorticotrophic hormone (ACTH) stimulation testing concerning the effects of steroids and no increase in steroid-associated adverse events. Low-dose steroids appear to improve mortality rates in patients with septic shock who are at high risk of death; however, additional trials in this subpopulation are necessary to definitively determine the role of low-dose steroids during sepsis.

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Section: Resultssupporting

confidence: 78%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The effects of steroids during sepsis depend on dose and severity of illness: an updated meta-analysis

Minneci

Deans

Eichacker

et al. 2009

Clinical Microbiology and Infection

109

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“…Three LOE 5 randomized controlled trials in adults with vasopressor-dependent septic shock 457,462,463 showed that survival was improved when low-dose hydrocortisone was administered, while 1 small adult LOE 5 randomized controlled trial 464 showed a trend toward increased survival.…”

Section: Arrhythmia Therapypeds-030mentioning

confidence: 99%

Part 10: Pediatric Basic and Advanced Life Support

Kleinman

Caen

Chameides³

et al. 2010

Circulation

183

184

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Note From the Writing Group: Throughout this article, the reader will notice combinations of superscripted letters and numbers (eg, “Family Presence During ResuscitationPeds-003”). These callouts are hyperlinked to evidence-based worksheets, which were used in the development of this article. An appendix of worksheets, applicable to this article, is located at the end of the text. The worksheets are available in PDF format and are open access.

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“…The odds of mortality (four studies [8,36,42,45]), for both corticotrophin responders and non-responders was not significantly different compared with control (Table 5). …”

Section: Resultsmentioning

confidence: 99%

Updating the evidence for the role of corticosteroids in severe sepsis and septic shock: a Bayesian meta-analytic perspective

et al. 2010

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IntroductionCurrent low (stress) dose corticosteroid regimens may have therapeutic advantage in severe sepsis and septic shock despite conflicting results from two landmark randomised controlled trials (RCT). We systematically reviewed the efficacy of corticosteroid therapy in severe sepsis and septic shock.MethodsRCTs were identified (1950-September 2008) by multiple data-base electronic search (MEDLINE via OVID, OVID PreMedline, OVID Embase, Cochrane Central Register of Controlled trials, Cochrane database of systematic reviews, Health Technology Assessment Database and Database of Abstracts of Reviews of Effects) and hand search of references, reviews and scientific society proceedings. Three investigators independently assessed trial inclusion and data extraction into standardised forms; differences resolved by consensus.ResultsCorticosteroid efficacy, compared with control, for hospital-mortality, proportion of patients experiencing shock-resolution, and infective and non-infective complications was assessed using Bayesian random-effects models; expressed as odds ratio (OR, (95% credible-interval)). Bayesian outcome probabilities were calculated as the probability (P) that OR ≥1. Fourteen RCTs were identified. High-dose (>1000 mg hydrocortisone (equivalent) per day) corticosteroid trials were associated with a null (n = 5; OR 0.91(0.31-1.25)) or higher (n = 4, OR 1.46(0.73-2.16), outlier excluded) mortality probability (P = 42.0% and 89.3%, respectively). Low-dose trials (<1000 mg hydrocortisone per day) were associated with a lower (n = 9, OR 0.80(0.40-1.39); n = 8 OR 0.71(0.37-1.10), outlier excluded) mortality probability (20.4% and 5.8%, respectively). OR for shock-resolution was increased in the low dose trials (n = 7; OR 1.20(1.07-4.55); P = 98.2%). Patient responsiveness to corticotrophin stimulation was non-determinant. A high probability of risk-related treatment efficacy (decrease in log-odds mortality with increased control arm risk) was identified by metaregression in the low dose trials (n = 9, slope coefficient -0.49(-1.14, 0.27); P = 92.2%). Odds of complications were not increased with corticosteroids.ConclusionsAlthough a null effect for mortality treatment efficacy of low dose corticosteroid therapy in severe sepsis and septic shock was not excluded, there remained a high probability of treatment efficacy, more so with outlier exclusion. Similarly, although a null effect was not excluded, advantageous effects of low dose steroids had a high probability of dependence upon patient underlying risk. Low dose steroid efficacy was not demonstrated in corticotrophin non-responders. Further large-scale trials appear mandated.

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Physiological-dose steroid therapy in sepsis [ISRCTN36253388]

Cited by 147 publications

References 43 publications

The effects of steroids during sepsis depend on dose and severity of illness: an updated meta-analysis

The effects of steroids during sepsis depend on dose and severity of illness: an updated meta-analysis

Part 10: Pediatric Basic and Advanced Life Support

Updating the evidence for the role of corticosteroids in severe sepsis and septic shock: a Bayesian meta-analytic perspective

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