Why did sterile salt water become the IV fluid of choice?

During a recent walk around the emergency room where I work, I noted the number of patients with bags of intravenous fluids hanging above them. Almost everyone had one.

Our ER in Boston isn't unique. IV fluids are among the most common medical interventions worldwide. Several kinds are available, but one called normal saline is by far the most popular. Over 200 million liters are used every year in the United States.

Primarily a treatment for dehydration, normal saline is given without a second thought for a variety of conditions, from vomiting to fast heart rates to lightheadedness.

For such a ubiquitous treatment, you'd probably expect that saline has been thoroughly studied and refined. As it turns out, that was never really the case at all. Now there's a rethinking about whether saline is really the best way to go.

Intravenous fluids were invented in England in the first decades of the 19th century to treat cholera, which even then was recognized as a disease that killed by dehydration. Early physicians knew that human blood was salty, and a Scottish doctor named Latta developed a primitive salt water solution to replace through the veins what had been lost through the bowels. The effect was "remarkable," according to The Lancet in 1832.

By the 1880s, scientists knew more about the basic chemical elements in human blood. A physiologist named Sidney Ringer created a solution containing sodium, potassium, and chloride in concentrations similar to blood. It's still in use today. We call it lactated Ringer's solution.

Ringer's solution was slow to catch on, though, and a simpler salt solution known as normal saline became the de facto IV fluid of the early 20th century. A descendent of Latta's original fluid, normal saline contains only two ingredients — water and salt.

The origin of normal saline has been traced to an 1883 study by a Dutch scientist named Hamburger. His work suggested, mistakenly, that the concentration of salts in human blood was 0.9 percent. He argued that a solution of equal concentration would be a "normal" composition for intravenous fluids, hence the name. Amazingly, the ascendance of normal saline as the default IV fluid seems to have been based solely on Hamburger's early experiments. "It remains a mystery how it came into general use as an intravenous fluid," a group of British physicians wrote in 2008, noting the absence of any other experimental data to support it. "Perhaps it was due to the ease, convenience, and low cost of mixing common salt with water."

As it turns out, normal saline isn't very normal at all. The average sodium level in a healthy patient is about 140 (as measured in something called milliequivalents per liter). For chloride, it's about 100. But the concentration of both sodium and chloride in normal saline is 154. That's pretty abnormal—especially the chloride.

It wasn't until the 1980s that researchers began investigating whether the higher concentrations of chloride might have adverse effects. In 1983 a scientist showed that elevated levels of chloride could decrease blood flow in dog kidneys, causing damage or even renal failure. And in the 1990s, scientists showed the high level of chloride in normal saline could make blood acidic, a change than can disrupt all kinds of biochemical processes in the body.

But did changes like these affect how patients fared?

Serious efforts to answer that question only got underway within the last 10 years. The first attempt appeared in 2012. Researchers examined a database of patients who received saline or balanced solutions like lactated Ringer's during surgery, and compared complications and mortality between the groups. The findings were striking — mortality was 2.7 percent higher in those that received normal saline, and complications were more common as well. That same year, Australian physicians showed that ICU patients given chloride-rich fluids had nearly double the rate of kidney injury compared with those given balanced fluids. In 2013 a study showed increased mortality and longer hospital stays among surgical patients receiving normal saline. And the following year, researchers at Duke found that sepsis patients had a 3 percent increase in mortality when treated with saline rather than balanced fluids.

All of these studies had limitations, and none were the kind of randomized, controlled trials that represent that gold standard for uncovering scientific truth.

But a study published this month in the New England Journal of Medicine may have "moved the needle," according to lead author Dr. Matthew Semler. With colleagues at Vanderbilt, Semler studied 15,000 ICU patients randomly assigned to receive normal saline or balanced fluids like lactated Ringer's, and found that those in the latter group did a bit better.

The researchers measured a combined outcome of death, need for dialysis, or persistent kidney problems. About 14 percent of patients receiving balanced fluids experienced this outcome, compared with about 15 percent for those receiving saline.

How important is a difference of 1 percentage point?

"Given two solutions that are equally available, equal in cost and that millions of adults receive every year, 1 percent is pretty good," Semler told me. "We'd be lucky to improve mortality by 1 percent with an expensive drug, much less a fluid that costs $2."

He took another tack to illustrate the importance of the study's findings. "There are 5 million patients admitted to an ICU in the United States every year," he said. "For every 100 patients treated with balanced fluids instead of saline, 1 less patient would experience death, new dialysis, or persistent renal problems."

That is pretty good, especially when you consider that 125 patients need to take blood pressure medications for 5 years to prevent one fatal stroke. Or that more than 1,600 healthy patients need to take an aspirin for a year to prevent a single heart attack.

"Because tens of millions of patients receive these fluids every year in the United States, just shifting the default from normal saline to balanced fluids has the potential to change outcomes for huge numbers of patients," he said, "much more so than most new blockbuster drugs."

I'm inclined to share his enthusiasm. Next time I give a patient IV fluids, I think I'll reach for the Ringer's.

Clayton Dalton is a resident physician at Massachusetts General Hospital in Boston. Copyright 2019 NPR. To see more, visit https://www.npr.org.