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| Study (year) | Location | Design | No. of research centres | No. of participants | Participants | Age
corticosteroids vs placebo | Male
corticosteroids vs placebo | Interventions | Clinical outcomes |
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| Sprung et al,1984 | USA | Multicentre double blind randomised placebo controlled trial | 2 | 59 | Adults
Vasopressor dependent shock | 55(4) vs 48(4) | 36% vs 10% | Dexamethasone 6mg/kg
Methylprednisolone 30mg/kg
Doses could be repeated | Hospital mortality, shock reversal, complications of septic shock, and adverse events |
|
| Bone et al, 1987 | USA | Multicentre double blind randomised placebo controlled trial | 19 | 382 | Adults
With sepsis (n=234) OR
Septic shock (n=148) | 53(16) vs 53.7(16) | NA | Methylprednisolone 30mg/kg
Every 6 hours
Duration: 24hrs | For septic shock: shock reversal, 14-d mortality, and adverse events |
|
| Luce et al, 1988 | USA | Single-centre double blind randomised placebo controlled trial | 1 | 75 | Adults (n=75)
Sepsis AND septic shock | 50(2.5) vs 53(2.5) | 68.4% vs 83.8% | Methylprednisolone
30mg/kg every 6hrs
Duration: 1 day | Prevention of ARDS and hospital mortality |
|
| Bollaert et al, 1998 | France | Multicentre double blind randomised placebo controlled trial | 2 | 41 | Adults
Vasopressor AND ventilator dependent septic shock | 66(21,83) vs 56(34,81) | 68.2% vs 63.2% | Hydrocortisone 100mg
Every 8hrs
Duration:
5 days then tapered over 6 days | Shock reversal, 28-d, ICU and hospital mortality, improvement in haemodynamics, ICU and hospital LoS, and adverse events |
|
| Briegel et al, 1999 | Germany | Single-centre double blind randomised placebo controlled trial | 1 | 40 | Adults Vasopressor AND Ventilator dependent septic shock | 47(4) vs 51(5) | 45% vs 60% | Hydrocortisone 100mg loading
0.18mg/kg/hr maintenance
Duration:
Until shock reversal, then tapered off | Shock reversal, 28-d, hospital and ICU mortality, Improvement in haemodynamics, ICU and hospital LoS, and adverse events |
|
| Chawla et al, 1999 | USA | Single-centre double blind randomised placebo controlled trial | 1 | 44 | Adults
Vasopressor dependent shock | NA | NA | Hydrocortisone 100mg
Every 8hrs
Duration: 3 days then tapered over 4 days | Shock reversal, 28-d and hospital mortality, improvement in haemodynamics, ICU LoS, and adverse events |
|
| Annane et al, 2002 | France | Multicentre double blind randomised placebo controlled trial | 19 | 300 | Adults
Vasopressor AND Ventilator dependent septic shock. | 60(17) vs 62(15) | 70% vs 64% | Hydrocortisone 50mg Every 6hrs
AND Fludrocortisone 50mcg Every 24hrs
Duration 7 days | 28-d, ICU, hospital and 1-y mortality, shock reversal, organ system failure free days, ICU and hospital LoS, and adverse events |
|
Oppert et al,
2005 | Germany | Single-centre double blind randomised placebo controlled trial | 1 | 40 | Adults
Vasopressor dependent septic shock | 59 vs 47 | 72% vs 83% | Hydrocortisone
Load: 50mg
Maint: 0.18mg/kg/hr
Duration: until stopping vasopressor
0.06mg/kg/hr for 1 day then reduced by 0.02mg/kg/hr every day | Shock reversal, 28-d mortality, cytokine response, and SOFA score |
|
| Mussack et al, 2005 | | Single-centre double blind randomised placebo controlled trial | 1 | 24 | Adults
Vasopressor dependent septic shock | 41(30,52) vs
54 (47,57) | 58% vs 50% | Hydrocortisone
Load: 100mg
Maint: 0.18 mg/kg/h for Duration 6 days. | 28-d mortality and shock reversal |
|
| Cicarelli et al, 2007 | Brazil | Single-centre double blind randomised placebo controlled trial | 1 | 29 | Adults
Vasopressor dependent septic shock | 69(11) vs 61(15) | 42.9% vs 46.7% | Dexamethasone 0.2mg/kg
Every 36hrs
Duration: 3 doses | 28-d mortality
Duration of vasopressor support
Duration of mechanical ventilation |
|
| Sprung et al, 2008 | Europe
Israel | Multicentre double blind randomised placebo controlled trial | 52 | 499 | Adults
Septic shock | 63(14) vs 63(15) | 34% vs 33% | Hydrocortisone
50mg every 6hrs – 5 days
50mg every 12hrs – 3 days
50mg every day – 3 days | 28-d, ICU hospital and 1-y mortality, shock reversal, organ failure–free days, and adverse events |
|
| Hu et al, 2009 | China | Single-centre double blind randomised placebo controlled trial | 1 | 77 | Adults
Septic shock | 56.17(33.85) vs 54.91(35.36) | 61% vs 64% | Hydrocortisone 50mg every 6hrs for 7 days
50mg every 8hrs for 3 days
50mg every 12hrs for 2 days
50mg every 24hrs for 2 days | Time on noradrenaline lactate clearance and ICU mortality and ICU LoS, and shock reversal |
|
| Arabi et al, 2010 | Saudi Arabia | Single-centre double blind randomised placebo controlled trial | 1 | 75 | Adults
Liver cirrhosis and septic shock | 60.6(12.6) vs 59.3(12.2) | 44% vs 44% | Hydrocortisone 50mg
Every 6hrs
Duration: Until shock resolution then tapered by 10mg every 48hrs until stopped | 28-d, ICU and hospital mortality, shock reversal, mechanical ventilation free days, RRT free days, ICU and hospital LoS, SOFA Score at d7, and adverse events |
|
| Gordon et al, 2014 | UK | Multicentre prospective open-label randomized controlled pilot trial | 4 | 61 | Adults
Septic shock treated with vasopressor | 61 (54, 68) vs
60 (48, 76) | 58% vs 60% | Hydrocortisone 50mg
Every 6 hours for 5 days
Every 13hrs for 3 days
Every 24hrs for 3 days | Vasopressin requirements, 28-d, ICU and hospital mortality, organ failure free days, shock reversal, ICU and hospital LoS, and adverse events |
|
| Póvoa et al, 2015 | Portugal | Multicentre double blind randomised placebo controlled trial | ? | 1695 | Adults
Septic shock treated with vasopressor | For DrotAA +
steroid vs DrotAA+ steroid: 64.4 (52.5, 74.2) vs 66.2 (55.4, 76.0).
For placebo +steroid vs placebo: 66.2 (54.5, 76.6) vs 63.6 (51.4, 75.2) | For DrotAA +
steroid vs DrotAA:56.4% vs 59.2%.
For placebo +steroid vs placebo:54.1% vs 56.1%. | DrotAA 24 μg/kg/hour and steroids at baseline.
Placebo and steroids at baseline | 28-d and 90-d mortality, SOFA Score |
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| Gordon et al, 2016 | UK | Multicentre double blind randomised placebo controlled trial | 18 | 409 | Adults
Septic shock | For vasopressin+ hydrocortisone vs vasopressin+ Placebo: 66 (57,76) vs 67 (59,77).
For norepinephrine
+ Hydrocortisone vs Norepinephrine
+ Hydrocortisone+ Placebo: 63 (52,76) vs 63 (52,76). | For vasopressin+ hydrocortisone vs vasopressin+ Placebo: 58% vs 50%.
or norepinephrine
+ Hydrocortisone vs Norepinephrine
+ Hydrocortisone+ Placebo: 61% vs 63%. | hydrocortisone 50 mg Every 6 hours for 5 days Every 12 hours for 3 days
Once daily for 3 days | kidney failure–free days, rates and duration of renal replacement therapy, 28-d, ICU and hospital mortality, SOFA Score, and adverse events |
|
| Tongyoo et al, 2016 | Bangkok | Single-centre double blind randomised placebo controlled trial | 1 | 197 | Adults
With sever sepsis (n=43) OR Septic shock (n=154) | 64.5(17.3) vs 64.3(16.0) | 51% vs 51.5% | hydrocortisone 50 mg Every 6 h daily for 7 days. | 28-d and 60-d mortality and 28-day survival without organ support |
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| Lv et al, 2017 | China | Single-centre double blind randomised placebo controlled trial | 1 | 118 | Adults
Septic shock treated with norepinephrine | 68.8(12.6) vs 64.8(16.7) | 55.2% vs 61.7% | hydrocortisone 200 mg/d for 6 days
100mg/d for 3 days
50mg/d for 3 days | 28-d and hospital mortality, shock reversal, ICU and hospital LoS |
|
| Doluee et al, 2018 | Iran | Single-centre double blind randomised placebo controlled trial | 1 | 160 | Adults
refractory septic shock treated with vasopressor | 67.13(10.92) vs 66.93(11.2) | 58.8% vs 41.3% | Hydrocortisone 50mg iv every 6 hours for 7 days | 28-d mortality and return of shock |
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| Annane et al, 2018 | France | Multicentre double blind randomised placebo controlled trial | 18 | 1241 | Septic shock treated with vasopressor | 66(14) vs 66(15) | 65.5% vs 67.7% | hydrocortisone 50 mg/d for 6h and fludrocortisone days 50μg once daily for 7 days | 90-d, 28-d,180-d, ICU discharge and hospital mortality, shock reversal, the time to weaning from mechanical ventilation, mechanical ventilation free days, ICU and hospital LoS, SOFA Score, and adverse events |
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| Venkatesh et al, 2018 | Australia and New Zealand | Multicentre double blind randomised placebo controlled trial | 3 | 3658 | Septic shock treated with vasopressor and undergoing mechanical ventilation | 62.3(14.9) vs 62.7(15.2) | 60.4% vs 61.3% | hydrocortisone 200mg /d for 7 days | 90-d, 28-d, ICU and hospital mortality, shock reversal, the frequency and duration of mechanical ventilation and RRT, ICU and hospital LoS, receipt of
blood transfusion and adverse events |
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