I recall grillings about intravenous (IV) fluids and the compartments of the body as a very junior doctor. Confidence in prescribing the right fluid, at the right rate at the right time, with or without added potassium, seemed to be the mark of a registrar. Amid the anxiety provoked by on-call ward cover—a stack of dog eared fluid charts, obs charts, blood charts, and their corresponding patients—it felt difficult to see the wood for the trees when charting fluid prescriptions. Had I thought in a more rational manner, I might have asked for a clearer overview of the wood before I got lost in the detail and day to day of the trees.

Whether you are interested in the big IV fluid wood or the detail of its many trees—in evidence, regulation, or understanding more about fluids—this story about how we got to where we are with hydroxyethyl starch solutions (HES) should make a thought provoking read.

German researchers and intensivists Christiane Hartog and colleagues explain that HES was licensed based on small studies in the 1970s, which would probably not pass muster today. Newer versions were added over time. Harms began to emerge soon after licensing, but the body of evidence remained favourable. About half of a hundred reviews were authored or co-authored by corporate funded investigators, they write. And the authors explain how unfavourable evidence was marginalised.

From 2008, with the expectation that HES would be helpful, three large trials examined the benefits and harms of HES. Speaking to us in an accompanying podcast, Hartog describes how all these large studies on HES, with patient relevant outcomes and a reasonable follow-up (around three months), show consistent harm.

In 2013 the US regulator, the Food and Drug Administration (FDA), issued a “black box warning” for HES about mortality and renal injury, and advised it should not be used in critically ill populations. The European Medicines Agency (EMA) decided to pull HES entirely. Some manufacturers requested that the EMA look again.

In the meantime, countries including the UK took independent action to withdraw HES. This action triggered a second review by the EMA and a new decision from a second committee allowed continued use in some populations, such as trauma and elective surgery patients. The second conclusion called for further research, but Hartog and colleagues question whether such research is feasible or ethical. They think that the license should be withdrawn while these studies are conducted.

If IV fluids were a new invention today, I wonder whether our understanding would evolve differently? I wonder what fluids on-call doctors are prescribing on the wards today? And what various specialties and their registrars are discussing about the data and debate on the harms of HES . . .

Helen Macdonald is the analysis editor, The BMJ.