Low-dose corticosteroids for adult patients with septic shock: a systematic review with meta-analysis and trial sequential analysis

Rygård, Sofie Louise; Butler, Ethan; Granholm, Anders; Møller, Morten Hylander; Cohen, Jérémy; Finfer, Simon; Perner, Anders; Myburgh, John; Venkatesh, Balasubramanian; Delaney, Anthony

doi:10.1007/s00134-018-5197-6

Cited by 166 publications

(190 citation statements)

References 45 publications

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“…In a recent systematic review, the pooled estimate relative risk (RR) for mortality (within 90 days) with low-dose corticosteroids in adult patients with septic shock was 0.96 (95% CI 0.91-1.02). 56 Several factors may contribute to the heterogeneity observed in these study results. First is the difference in patient population and the severity of illness.…”

Section: Low-dose Corticosteroidsmentioning

confidence: 91%

“…The most concerning adverse effects when used in the setting of septic shock are related to corticosteroid effects on the immune system (e.g., secondary infection), the gastrointestinal system (e.g., gastrointestinal bleeding), and metabolic effects (e.g., hyperglycemia, hypernatremia). In one meta‐analysis, no difference in the risk for secondary infections (RR 1.05, 95% CI 0.95–1.16) or gastrointestinal bleeding (RR 1.09, 95% CI 0.8–1.46) was observed, but risk for hyperglycemia (RR 1.11, 95% CI 1.07–1.16) and hypernatremia (RR 1.67, 95% CI 1.35–2.07) was higher with corticosteroids . A second meta‐analysis demonstrated an increased risk for hypernatremia (RR 1.64, 95% CI 1.32–2.03), hyperglycemia (RR 1.16, 95% CI 1.08–1.24), and neuromuscular weakness (RR 1.21, 95% CI 1.01–1.52) with steroid administration .…”

Section: Corticosteroidsmentioning

confidence: 98%

“…The impact of steroids on mortality, however, is mixed. In a recent systematic review, the pooled estimate relative risk (RR) for mortality (within 90 days) with low‐dose corticosteroids in adult patients with septic shock was 0.96 (95% CI 0.91–1.02) …”

Section: Corticosteroidsmentioning

confidence: 99%

“…Despite the numerous RCTs and more than 60 years of experience with using corticosteroids in shock, several unanswered questions still remain. First, the role of fludrocortisone remains unclear, although there may be some benefit in patients who are at high risk of death . Future studies are needed across the spectrum of illness severity.…”

Section: Corticosteroidsmentioning

confidence: 99%

“…62 In a subgroup analysis from a recent meta-analysis, steroid administration technique did not influence survival. 56…”

Section: Low-dose Corticosteroidsmentioning

confidence: 99%

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Catecholamine Vasopressor Support Sparing Strategies in Vasodilatory Shock

et al. 2019

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Shock syndromes are associated with unacceptably high rates of mortality in critically ill patients despite advances in therapeutic options. Vasodilatory shock is the most common type encountered in the intensive care unit. It is manifested by cardiovascular failure, peripheral vasodilatation, and arterial hypotension leading to tissue hypoperfusion and organ failure. Hemodynamic support is typically initiated with fluid resuscitation strategies and administration of adrenergic vasopressor agents in nonresponsive patients to restore arterial pressure with subsequent adequate organ reperfusion. Unfortunately, high catecholamine dosing requirements may be necessary to achieve targeted hemodynamic goals that may increase the risk of vasopressor‐induced adverse events. The purpose of this article is to review the clinical efficacy and safety data and potential role in therapy for catecholamine‐sparing agents in vasodilatory shock. Adjunctive therapeutic options to reduce vasoactive support requirements without compromising arterial pressure include arginine vasopressin and analogs, corticosteroids, midodrine, methylene blue, and angiotensin II. Although concomitant vasopressin and corticosteroids have a more defined role in evidence‐based guidelines for managing shock, clinicians may consider other potential catecholamine‐sparing agents.

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Section: Low-dose Corticosteroidsmentioning

confidence: 91%

Section: Corticosteroidsmentioning

confidence: 98%

Section: Corticosteroidsmentioning

confidence: 99%

Section: Corticosteroidsmentioning

confidence: 99%

“…62 In a subgroup analysis from a recent meta-analysis, steroid administration technique did not influence survival. 56…”

Section: Low-dose Corticosteroidsmentioning

confidence: 99%

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Catecholamine Vasopressor Support Sparing Strategies in Vasodilatory Shock

et al. 2019

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Association of Corticosteroid Treatment With Outcomes in Adult Patients With Sepsis

et al. 2019

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IMPORTANCEAlthough corticosteroids are widely used for adults with sepsis, both the overall benefit and potential risks remain unclear.OBJECTIVE To conduct a systematic review and meta-analysis of the efficacy and safety of corticosteroids in patients with sepsis. DATA SOURCES AND STUDY SELECTION MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception until March 20, 2018, and updated on August 10, 2018. The terms corticosteroids, sepsis, septic shock, hydrocortisone, controlled trials, and randomized controlled trial were searched alone or in combination. Randomized clinical trials (RCTs) were included that compared administration of corticosteroids with placebo or standard supportive care in adults with sepsis.DATA EXTRACTION AND SYNTHESIS Meta-analyses were conducted using a random-effects model to calculate risk ratios (RRs) and mean differences (MDs) with corresponding 95% CIs. Two independent reviewers completed citation screening, data abstraction, and risk assessment. MAIN OUTCOMES AND MEASURES Twenty-eight-day mortality.RESULTS This meta-analysis included 37 RCTs (N = 9564 patients). Eleven trials were rated as low risk of bias. Corticosteroid use was associated with reduced 28-day mortality (RR, 0.90; 95% CI, 0.82-0.98; I 2 = 27%) and intensive care unit (ICU) mortality (RR, 0.85; 95% CI, 0.77-0.94; I 2 = 0%) and in-hospital mortality (RR, 0.88; 95% CI, 0.79-0.99; I 2 = 38%). Corticosteroids were significantly associated with increased shock reversal at day 7 (MD, 1.95; 95% CI, 0.80-3.11) and vasopressor-free days (MD, 1.95; 95% CI, 0.80-3.11) and with ICU length of stay (MD, −1.16; 95% CI, −2.12 to −0.20), the sequential organ failure assessment score at day 7 (MD, −1.38; 95% CI, −1.87 to −0.89), and time to resolution of shock (MD, −1.35; 95% CI, −1.78 to −0.91). However, corticosteroid use was associated with increased risk of hyperglycemia (RR, 1.19; 95% CI, 1.08-1.30) and hypernatremia (RR, 1.57; 95% CI, 1.24-1.99). CONCLUSIONS AND RELEVANCEThe findings suggest that administration of corticosteroids is associated with reduced 28-day mortality compared with placebo use or standard supportive care. More research is needed to associate personalized medicine with the corticosteroid treatment to select suitable patients who are more likely to show a benefit.

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Comparative Effectiveness of Fludrocortisone and Hydrocortisone vs Hydrocortisone Alone Among Patients With Septic Shock

et al. 2023

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ImportancePatients with septic shock may benefit from the initiation of corticosteroids. However, the comparative effectiveness of the 2 most studied corticosteroid regimens (hydrocortisone with fludrocortisone vs hydrocortisone alone) is unclear.ObjectiveTo compare the effectiveness of adding fludrocortisone to hydrocortisone vs hydrocortisone alone among patients with septic shock using target trial emulation.Design, Setting, and ParticipantsThis retrospective cohort study from 2016 to 2020 used the enhanced claims-based Premier Healthcare Database, which included approximately 25% of US hospitalizations. Participants were adult patients hospitalized with septic shock and receiving norepinephrine who began hydrocortisone treatment. Data analysis was performed from May 2022 to December 2022.ExposureAddition of fludrocortisone on the same calendar day that hydrocortisone treatment was initiated vs use of hydrocortisone alone.Main Outcome and MeasuresComposite of hospital death or discharge to hospice. Adjusted risk differences were calculated using doubly robust targeted maximum likelihood estimation.ResultsAnalyses included 88 275 patients, 2280 who began treatment with hydrocortisone-fludrocortisone (median [IQR] age, 64 [54-73] years; 1041 female; 1239 male) and 85 995 (median [IQR] age, 67 [57-76] years; 42 136 female; 43 859 male) who began treatment with hydrocortisone alone. The primary composite outcome of death in hospital or discharge to hospice occurred among 1076 (47.2%) patients treated with hydrocortisone-fludrocortisone vs 43 669 (50.8%) treated with hydrocortisone alone (adjusted absolute risk difference, −3.7%; 95% CI, −4.2% to −3.1%; P &lt; .001).Conclusions and RelevanceIn this comparative effectiveness cohort study among adult patients with septic shock who began hydrocortisone treatment, the addition of fludrocortisone was superior to hydrocortisone alone.

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Low-dose corticosteroids for adult patients with septic shock: a systematic review with meta-analysis and trial sequential analysis

Abstract: In adults with septic shock treated with low dose corticosteroids, short- and longer-term mortality are unaffected, adverse events increase, but duration of shock, mechanical ventilation and ICU stay are reduced. PROSPERO registration no. CRD42017084037.

Cited by 166 publications

References 45 publications

Catecholamine Vasopressor Support Sparing Strategies in Vasodilatory Shock

Catecholamine Vasopressor Support Sparing Strategies in Vasodilatory Shock

Association of Corticosteroid Treatment With Outcomes in Adult Patients With Sepsis

Comparative Effectiveness of Fludrocortisone and Hydrocortisone vs Hydrocortisone Alone Among Patients With Septic Shock

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