A trainee has pointed out that this might be useful. Readers are reminded of numerous other (better) resources which compile this information, of which the best has to be Critical Care Reviews. Still, there seemed to be some merit in creating a list for quick reference. Wherever possible, the links of the trial eponym or author reference lead to a free full text version of the paper, and the year is a link to the corresponding page at The Bottom Line.
Early goal-directed therapy in sepsis
Rivers et al - 2001 - EGDT in Detroit; n=268. A trial of protocolised care for sepsis, vs. apparently no care at all (as the mortality difference was stark: 29.2% vs 44.4%).
ProCESS - 2014 - EGDT around US; n= 1,351. A faithful reenactment of the River's trial; no difference in mortality (18.2% vs 18.9%)
ARISE - 2014 - EGDT around Australia and NZ; n=1600. No difference in mortality (18.6% vs. 18.8%); patients were largely rather less sick
ProMISE - 2015 - EGDT around the UK; n=1260. No difference in mortality (29.5% vs. 29.2%); the main difference between groups was SvO2 and CVP guided management.
ANDROMEDA-SHOCK - 2018 - goals: lactate vs cap refill time; n=424, from Central America. Mortality was higher in the lactate group (43.4% vs 34.9%), but not statistically significant, plus for some reason they used 28-day mortality.
Vasopressors in sepsis
CATS - 2007 - adrenaline vs. noradrenaline+dobutamine; n=330 in France. No mortality difference (47% vs 44%), nor any difference in adverse events.
Myburgh - 2008 - adrenaline vs noradrenaline, with MAP goals as the primary outcome. n=280 in Australia. No difference (a pressor is a pressor) but 12.9% dropped out of the adrenaline arm for "significant but transient metabolic effects".
VASST - 2016 - noradrenaline and vasopressin? n=802 in Canada, Australia, US. No difference in mortality (35.4% vs 39.3%), but the patients were not especially sick.
VANISH - 2016 - does early vasopressin prevent AKI? n=409, in the UK. No, it does not (56.8% vs 59.7% went dialysis-free)
CENSER - 2019 - but what if early norad, and peripherally? n=310, single centre in Thailand. Shock resolved faster in 76.1% vs 48.4% (mortality 15.5% vs 21.9%)
Albumin in sepsis
SAFE - 2004 - not really a sepsis study, just saline vs albumin (n=6997 in Australia). Septic subgroup (n=1218) found better mortality (30.7% vs 35.3%) on post-hoc analysis.
ALBIOS - 2014 - but what if albumin was kept over 30? n=1818 in Italy. No difference in mortality (31.8% vs 32.0%), using 20% albumin.
ALPS - 2022 - what if albumin, but only in cirrhotic septic patients? n=100, in India. No difference in mortality (58% vs 62%), just faster resolution of hypotension.
Steroids in sepsis
CORTICUS - 2008 - hydrocortisone 50mg qid; n=499, in Europe. No difference in mortality (34.3% vs. 31.5%) but shock reversed much faster (3.2 vs 5.4 days).
COIITSS - 2010 - what if steroids and intensive insulin therapy (which we now know doesn't work)? n=509, in France. Unsurprisingly it didn't work (45.9% vs 42.9%).
HYPRESS - 2016 - but what if steroids before shock? n=380, in Germany. No difference in progression to shock (21.2% vs 22.9%); mortality was low (8.5%).
ADRENAL - 2018 - hydrocort infusion, n=3658 all over the world. No difference in mortality (27.9% vs 28.8%), but many secondary outcomes were improved (ICU LOS, ventilation time, shock resolution)
APROCCHSS - 2018 - but what if also fludrocortisone? n = 1241 in France. Mortality improved (43.0% vs 49.1%); these were extremely sick patients (1mcg/kg/min norad!)
CAPE COD - 2023 - steroids for severe community-acquired pneumonia without shock? n=800 in France. Improved mortality (6.2% vs 11.9%) especially if CRP was elevated to over 150.
Blood pressure targets in sepsis
SEPSISPAM - 2014 - is MAP of 85 necessary? n=776, in France. No difference in mortality (36.6% vs. 34%), but it did protect the kidneys of the chronically hypertensive patients (NNT=9.5), which is not nothing.
65 - 2020 - is MAP of 60 enough for the over-65s? n=1221, in the UK. No difference in mortality (41% vs 43.8%), so ... yes, it is enough. Survival was better for the chronically hypertensive group (38.2% vs. 44.3%) and trended higher the older you were.
Fluid resuscitation in sepsis
SOAP - 2006 - observational study of fluid use in European ICUs, n=3147. OR for mortality increased by 1.1 for every additional 1L of fluid balance in the first 72 hours.
FEAST - 2011 - fluid boluses vs. no boluses, in African children (n=3141) with mainly malaria (57%) who only got transfused if their Hb dropped below 50. Fluid bolus group had more mortality (10.5% vs 7.3%). Worth knowing because often referred to.
6S - 2012 - evil death-starch is bad for everyone, but what about sepsis? n=804, northern Europe. The answer is yes; it's still bad (higher risk of death, 51% vs 43%, as well as dialysis, 22% vs 16%)
TRISS - 2014 - what if Hb was over 90? n=1005, from Scandinavia. No difference in mortality (43% vs 45%); a Hb of 70 g/L is enough. They excluded acute coronary syndromes.
CLASSIC - 2022 - restrictive vs. liberal; n=1554, Denmark and Finland. No difference in mortality (42.3% vs 42.1%), but then again at 5 days both groups had a fluid balance around 8-10L.
CLOVERS - 2023 - liberal fluids vs early vasopressors; n=1563 in the US. No difference in mortality (14.0 vs 14.9%), or in adverse events.
Kumar - 2006 - the observational study from which SSG got their recommendation to give early antibiotics. n=2731 in Canada, US, Saudi Arabia. Mortality increased with every hour of delay following the onset of hypotension (by about 7.6%)
STOP-IT - 2015 - short course (4 days) of antibiotics in abdominal sepsis with good source control. n=517 in US and Canada. None of the primary outcomes were any worse with the short course.
BLING2 - 2015 - continuous vs intermittent β-lactams, n=432, Australia and NZ. No difference in any of the outcome measures (mortality 26% vs 28%) but also not powered to detect mortality differences.
BLISS - 2016 - continuous vs intermittent β-lactams; n=140 in Malaysia. Much higher cure rate (56% vs 34%) but no mortality benefit, and not blinded.
PRORATA - 2010 - procalcitonin used to guide antibiotics; n = 621 in France. 23% less antibiotic exposure, but the mortality difference favoured the control group (30% vs 26.1%), even though this did not reach statistical significance.
Guidelines for infectious diseases and sepsis
For antibiotic recommendations, the Australians should start with the electronic edition of the Therapeutic Guidelines. Many (most) of those working in Australia will have institutional access. The Sanford Guide is the next best option.
ISDA practice guideline list - a comprehensive set of recommendations, from which the following critical-care-relevant gems were mined:
ASID, the Australian version of the ISDA, have their own list of guidelines, but it is somewhat anaemic. Of interest are their guidelines on investigations and management of encephalitis.
CDC guideline list is excellent for:
Other guidelines in no specific institutional order: