Intravenous Fluids—A Test Case for Learning Health Systems

Abstract

Bledsoe and colleagues 1 present the results of the I USE LR study. This before-and-after study evaluated the outcomes associated with an implementation intervention promoting use of lactated Ringer solution rather than saline solution among nearly 150 000 patients across 22 hospitals. The intervention used education and changes to the electronic order entry system to affect which fluid patients received beginning immediately at hospital presentation. The proportion of intravenous fluid administered that was lactated Ringer increased (from approximately 25% to 75%) and the use of saline decreased (from approximately 75% to 25%). In interrupted time series analysis, implementation of lactated Ringer was associated with a 2% absolute risk reduction in death, new receipt of kidney replacement therapy, or persistent kidney dysfunction. This effect size was greater for patients with sepsis and patients who received more fluid. This study raises important questions about the choice between lactated Ringer and saline and, more broadly, how we should make evidence-based choices between widely available, commonly used treatment alternatives in acute care. What Magnitude of Difference in Clinical Outcomes Should Determine the Choice Between Two Available Treatments?Explanatory trials evaluating the efficacy and safety of adding a new drug or device to current clinical care (A vs A-plus) are traditionally powered to detect the smallest difference in clinical outcomes that would justify incorporating the new treatment into care, considering its added risks, costs, and burdens. For example, the median minimal clinically important difference in mortality targeted by acute care trials has been approximately 8%, implying that smaller differences in mortality might not justify incorporation of the new treatments into care. These types of trials ask, "is this new treatment better than current care by enough to offset the added cost and risk?" In contrast, when attempting to select between two treatments (A vs B) that are already extensively used in current care, widely available, and similar in cost, the concept of a minimal clinically important difference is less relevant.If availability and cost are similar, then the clinical question is simply, "which treatment is more likely to produce a better patient outcome?" The choice between balanced crystalloids and saline exemplifies such a comparative effectiveness question, and the unique challenges faced in determining which of two common treatments is better when essentially any difference in patient outcomes would be sufficient to drive practice.Balanced crystalloids (like lactated Ringer) and saline are the two commonly available options for intravenous isotonic crystalloid infusion. Both have been used for over a century, are widely available, and cost approximately $1 per liter to manufacture. More than 30 million patients in the United States receive these fluids each year. Because treatment with these fluids is so ubiquitous, differences in outcomes that might seem small at t...