Thread by @DogICUma

The @hrcNewZealand and @nhmrc funded #PLUStrial is the latest in a series of RCTs that have compared balanced crystalloids with saline in patients who are critically ill. It was published today in the @nejm nejm.org/doi/full/10.10…

Millions of litres of intravenous fluids are administered around the world every day. For patients who are acutely ill, small differences in mortality attributable to fluid choice would have profound global public health importance

We included 5037 patients from 53 ICUs in Australia & New Zealand. The primary end point was 90 day mortality. Day 90 mortality was 21.8% and 22% for balanced crystalloid and saline respectively (P=0.90).

The proportion of patients treated with new RRT was similar by treatment group (12.7% and 12.9% for balanced crystalloid & saline patients respectively.)

Our study participants received study fluids for longer & in greater volume than earlier trials. We achieved separation in key biochemical parameters that are hypothesized to mediate the adverse effects of saline.

While the study was stopped before reaching the intended recruitment target, we crossed a conservative stopping boundary that means it is extremely unlikely we would have observed a mortality effect of the size we had hypothesised if we had completed the trial.

Simultaneously published today in @NEJMEvidence with @naomihammond as first author is an updated systematic review and meta-analysis RCTS comparing balanced crystalloids with saline that incorporates the #PLUStrial data
evidence.nejm.org/doi/full/10.10…

We included 11 studies and 2 conference abstracts for a total of 35,884 trial participants. We adjudicated six studies with 34,450 participants as having a low risk of bias in all domains

Here is the summary of trials with low risk of bias:

A Bayesian meta-analysis for the low-risk-of-bias studies indicates an 89.5% probability that on average balanced crystalloids are associated with lower mortality compared with saline.

Given that balanced crystalloids and saline are widely available, and clinicians regularly need to choose between them, this analysis has important implications for practice

Balanced crystalloids are probably the best choice for fluid resuscitation in most critically ill patients

There is an important caveat because data suggest the possibility of harm with balanced crystalloids in patients with traumatic brain injury. Whether this risk extends to patients with other acute brain pathologies is unclear.

A patient-level meta-analysis should allow further evaluation of potential differential treatment effects in subpopulations (including patients with brain injuries). However, for now, balanced crystalloids are the logical choice for acutely ill adults without TBI.

Lots of great collaborators on this work including @f_g_zampieri @toddrice_ICU @JAMyburgh @NaomiHammond @rinaldobellomo @dianemackle @ClinResearchNZ @georgeinstitute

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