More Fuel For the Fluid Fire

Half a study likely misses out on the full effect.

Multiple randomized trials fail to find much difference between normal saline and “balanced” fluid solutions – but pooling those results favors balanced solutions, demonstrating a small, but real effect.

This is FLUID, a cluster-randomized crossover study in Canada in which hospitals replaced their default fluid for two twelve week periods. The main findings: “no difference.”

The main problem: COVID.

FLUID intended to enroll and crossover sixteen hospitals, but the onset of the COVID-19 pandemic limited enrollment to seven. Therefore, all the consistent tilting in favor of lactated ringer’s solution fails to reach statistical significance. Importantly, most of the difference in the composite outcome is driven by mortality, not readmission. Both are important patient-oriented endpoints, but one of those is a little more life-altering. There are also persisting concerns regarding the effect of balanced solution on mortality in traumatic brain injury, but this study does not enroll sufficient numbers to cast any light on this outstanding issue.

Interestingly, these effects also occurred despite lower compliance with giving lactated ringer’s during crossover periods – only 78% gave lactated ringers as directed, compared with 94% for saline.

Regardless, while these outcome measures are in the fractions of a percent – for a national health system, these tiny fractions add up to thousands of hospital readmissions per year. It is likely time to make balanced solutions the default, rather than the exception.