Thread by @Gas_Craic

What were the most impactful non-COVID papers over the past 2 years? Let's delve in and take a look. #SOA21

Finally an opportunity to not talk about COVID! #SOA21

TOMAHAWK - immediate vs delayed/selective angio. 3 years to conduct the trial in 31 ICUs. 554 patients. 'Worse' survival in immediate angiograph? Not SS, but close... #SOA21

TOMAHAWK - subgroup analysis .... no SS. Generally in favour of delayed angio though? WRT 30 day mortality. #SOA21 This is in OOHCA.... which brings us to...

Vasopressin + methylpred vs placebo on ROSC in IHCA. #SOA21 An important trial to challenge current practice. 501 patients randomised after 1st dose of adrenaline... Primary outcome ROSC for at least 20mins... Clear benefit in vaso+methylpred. #SOA21

Care post ROSC was not protocolised. Primary outcome was clearly SS. Secondary outcomes... well... for benefit/harm for longer term survival (30 days, or neuro recovery etc... is uncertain. #SOA21

Another trial that highlights the difficulties in these sorts of studies. If you don't control the 'rest' of care... post-resus etc - then how can we know? #SOA21

Now with fluids... #SOA21 BaSICS was published 2m ago. Saline v Balanced C.... first of all, remember 2018 SMART trial = >15000 patients. Composite outcome of MAKE30. Combined (I think) 3 outcomes to find a positive trial.... but in a subsequent analysis...

(2019) - looking at mortality... beneficial with balanced soln.

So this informed the SSG/SSC - and based on the 2019 analysis (and others) - statements were changed. BALANCED crystalloid instead of saline... #SOA21 So - back to BaSICS in 2021

Patients randomised (not ICU's), >11,000 patients. Randomised to either fluid (plasmalyte vs saline0.9). Key Q looked at mortality. #SOA21 - no significant difference... in fact...

No SS, but also trends to harm in TBI! So... back to the beginning... again. #SOA21

So... why so different? Median of 2.9L of study fluid (<1L of fluid per day).... also fluids prior to enrolment in trial... #SOA21 ?? Also different continents/environments.

Not all balanced solutions are equal? What about pH? #SOA21 Are any of them really 'physiological'? BaSICS were almost 50% post surgery.... So we still don't know.

Dare we move on to VICTAS? Patients with sepsis, randomised to VitC/Thia/Hydrocortisone v Control. Vent/Vaso-free days as outcome. No SS difference. #SOA21 No difference in mortality. No difference in anything really. 🤷

THIS IS CONSISTENT WITH THE OTHER MAJOR LITERATURE CONTRIBUTIONS. #SOA21 But... it didn't fully recruit the number of necessary patients, steroids allowed in both arms, heterogeneity in practice, no significant adverse events. 🤷

Still SSC/SSG suggest against using Vit C. #SOA21

Moving on. Too many sepsis pts lumped together... no phenotypes/microbes/molecular status looked at in detail... A massive heterogenous group bundled together in trials. #SOA21

AdrenOSS-2 trial. Adrecizumab. Binds to adrenomedullin (ADM). Protective role in the endothelial barrier. Regulates vascular tone. In sepsis, ADM can leak out of vasculature --> vasodilates and impairs endothelial barrier, incr perm. So the MAB stops this happening. #SOA21

4 Euro countries. Adults. Sepsis. Raised ADM level in vasculature. 2 different doses allocated. Feasibility and safety study. Lower SOFA score seen. No SS for mortality seen... Different approach seen in this trial! #SOA21 No signs of harm. More studies planned.

ETT cuff pressure control - continuous control v intermittent. To prevent VAP. 3 sites in Vietnam. 1500 patients screened - 600 randomised. No sig difference up to 13 weeks. Subgroups didn't reveal much either. #SOA21

How do we time RRT? >30 studies on early v late. >10 metanalysis... sometimes opposing conclusions! 4 RCTs - and now this trial #SOA21 only 278 randomised from 5336!! V.small group - niche. Thus, no SS in RRT-free days. Mort diff - no SS diff - hint towards higher mort in delayed

And so AKIKI-2 concluded.... but remember this was only a very small subgroup of patients. #SOA21

Final trial - ARDS-related: #SOA21 - vent-free days and mortality outcomes. Stopped early due to low recruitment. 5 years to 277 patients.... each site only randomised very infreq. Still - important results.

This would have probably gained more traction had it not been for COVID. #SOA21 Comments below:

Palliative Care: #SOA21

Personal views have tremendous impact... #SOA21