Question special

I thank the authors for conducting these outstanding pragmatic trials investigating this important and often overlooked issue regarding choice of IV fluids as current practice appears rooted in style (hospitalists and internists=saline; surgeons=LR; ICU=plasmalyte or normosol).

A few thoughts...

I wondered why the primary endpoints were different in the two studies. SALT-ED (noncritically ill) primarily examined hospital free days and secondarily examined major adverse kidney events while this was switched for SMART (critically ill).

For both studies, the composite outcome of major adverse kidney event is statistically significant (p=0.01 in SALT-ED; p=0.04 for SMART) however none of the components of the composite outcome are significantly different. How can this be?

I also calculated the "fragility index" for both studies. In short, the fragility index is calculated by considering a nonevent as an event until the statistical significance is lost. For SALT-ED, the fragility index=8 for major adverse kidney events, meaning if 8 patients in either group had this event then significance would be lost. For SMART, the fragility index=0. How are we to consider this in interpreting the findings?