Thread by @DogICUma

I am pleased & proud to see the #PLUStrial published in @NEJM today. It is my 10th @NEJM paper! Here’s my list of @NEJM papers and what I think they mean for clinical practice

#1: The #HEATtrial (Dec 2015) showed that using paracetamol to treat fever in ICU patients with suspected infections did not affect the number of ICU-free days. Mortality rates were similar in paracetamol & placebo-treated patients:
nejm.org/doi/full/10.10…

These data provide reassurance that if paracetamol is administered to treat fever in the setting of an infection or given for another reason to a patient who happens to have fever & infection, such as for analgesia, harm is unlikely to result.

#2: #TRICS3 (Nov 2017) showed that in moderate to high cardiac surgery, a restrictive transfusion strategy was not too much worse (i.e. was non-inferior) to a liberal strategy with respect to a composite of death, MI, stroke, or new dialysis
nejm.org/doi/full/10.10…

In patients 75yr or older, liberal transfusion was associated with worse outcomes. The TRICS III trial provides compelling evidence that a restrictive transfusion strategy is as effective & safe as a liberal strategy in cardiac surgery patients.

#3: The #ATHOS3trial (Dec 2017) showed that angiotensin-II increased blood pressure in patients with vasodilatory shock compared to placebo. Day 28 mortality was 46% in the angiotensin-II group and 54% in the placebo group (P=0.12).
nejm.org/doi/full/10.10…

This study led to the licensing of the 1st new class of vasopressor drug for vasodilatory shock for many years. I have never used angiotensin-II in practice because another trial to confirm or refute the potential mortality benefit is needed.

#4 Six month follow-up of the #TRICS3 trial (Sept 2018) looked at the same composite outcome as the primary trial but at six months and an extended composite that included EDs visits, hospitalisation, and coronary revascularisation.
nejm.org/doi/full/10.10…

The #TRICS trial six month follow-up confirmed that there is no advantage to liberal transfusion in moderate and high risk cardiac surgical patients.

#5 The #TARGETtrial (Nov 2018) compared energy-dense and routine enteral nutrition in critically ill patients. Energy-dense nutrition did not affect day 90 mortality but was associated with more GI intolerance. nejm.org/doi/full/10.10…

This trial challenges the dogma that achieving “target” calorie delivery in patients who are critically ill is an important determinant of patient outcomes. The #TARGETtrial suggests that hypocaloric & eucaloric feeding have similar effects on survival.

#6 The #ICUROXtrial (Mar 2020) compared the effect of conservative and liberal oxygen on ventilator-free days in adult patients who were anticipated to require mechanical ventilation beyond the day after enrolment. This was a neutral trial
nejm.org/doi/full/10.10…

The #ICUROXtrial represented an important reversal of previous data that suggested harm from liberal oxygen therapy and provided a degree of reassurance that usual (relatively liberal) provision of oxygen is not harmful. It also laid the foundation for the #MegaROX trial.

#7 #STARRT AKI (Jul 2020) compared accelerated and standard initiation of RRT in critically ill patients with AKI. Accelerated RRT did not reduce day 90 mortality compared to standard initiation of RRT and was associated with dialysis-dependence at day 90
nejm.org/doi/full/10.10…

The #STARRT AKI trial data provide strong support for an initial approach of “wait and see” in patients with AKI.

#8 Effect of Oxygen Therapy on Mortality in the ICU (editorial)
nejm.org/doi/full/10.10… This one, the editorial accompanying the #HOTICU trial is sort of cheating because it an editorial, but if I don’t count it I can’t get to 10 @nejm papers 

#9 #TTM2trial (Jun 2021) compared therapeutic hypothermia with normothermia in comatose cardiac arrest patients. At 6 months 50% in the hypothermia & 48% in the normothermia group died (P=0.37).
nejm.org/doi/full/10.10…

The #TTM2trial showed similar patient outcomes for hypothermia and normothermia overall and in all subgroups. Arrhythmias including VT were more common with hypothermia. Normothermia is the way to go.

#10 The #PLUStrial compared PlasmaLyte 148 ® with saline for IV fluid therapy in critically ill adults. There was no significant difference in 90 day mortality between groups and no difference in rates of renal failure requiring dialysis.
nejm.org/doi/full/10.10…

When the #PLUStrial data are added to data from other high quality RCTs we now have 34,450 patients randomised. Overall, it appears likely that balanced crystalloids reduce mortality overall and for ICU fluid therapy they should be the fluids of choice.
evidence.nejm.org/doi/full/10.10…

My contribution to many of these studies has been small and I am indebted to many excellent clinical researchers who have involved me in their excellent work including
@JAMyburgh @NaomiHammond @rinaldobellomo @dianemackle @drseanbagshaw @ronwald @nielsen_niklas @RichardWhitloc2

@sandrapeake01 @f_g_zampieri @toddrice_ICU @MelbourneICU @KhannaAshishCCM @CCCTG_ @anzicsCTG

I am also very grateful to the @HRCNewZealand who have provided (and continue to provide me) with the financial support that mean I can be an intensive care specialist who does some research.

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