Isotonic Fluids Without Potassium Could Be Harmful for Some Acutely Ill Kids

By Frederik Joelving

October 28, 2020

NEW YORK (Reuters Health) - A recent move to use isotonic rather than hypotonic intravenous fluids (IVFs) in acutely ill children could be boosting their risk of developing electrolyte disorders, a new trial suggests.

"Commercially available isotonic plasma-like fluids markedly increase the risk of hypokalemia in acutely ill children," said Dr. Terhi Tapiainen of Oulu University Hospital, in Finland, who led the research.

"Thus, they should not be used without adding extra potassium," she told Reuters Health by email. "Second, isotonic fluid therapy, with a high concentration of sodium, may slightly increase the risk of hypernatremia in acutely ill children."

Administration of hypotonic fluids was the de facto standard for years in pediatrics. But in December 2018 the American Academy of Pediatrics (AAP) issued a guideline recommending the use of isotonic solutions "with appropriate potassium chloride and dextrose" to prevent hyponatremia (https://bit.ly/2TpTxk3).

"There was a rapid shift towards the use of isotonic fluid therapy in children," Dr. Tapiainen explained. "Yet, there was little evidence on isotonic fluid therapy in acutely ill children. We were particularly concerned about the use of plasma-like isotonic fluids, with a low potassium concentration, because the risk of hypokalemia was not reported in earlier studies."

But Dr. Michael L. Moritz, a pediatric nephrologist at UPMC Children’s Hospital of Pittsburgh who worked on the AAP guideline, was highly critical of the work, saying the data did not support the authors' statement that "commercially available plasmalike isotonic fluids are not optimal for fluid therapy in acutely ill children."

"A more appropriate conclusion would be that 'plasmalike solution does not have sufficient potassium for children with gastroenteritis and hypokalemia,'" he told Reuters Health by email. "Isotonic fluids are the preferred intravenous solution to prevent hyponatremia and the addition of potassium chloride is helpful to correct and prevent hypokalemia, especially in children with gastroenteritis."

Between 2016 and 2019, Dr. Tapiainen and her colleagues randomly assigned 614 children between 6 months and 12 years of age to receive an isotonic solution available from Baxter as Plasmalyte Glucos 50 mg/ml or a moderately hypotonic solution.

Baxter's solution contained 140 mmol/L of sodium in 5% dextrose, 5 mmol/L of potassium, 1.5 mmol/L of magnesium, 98 mmol/L of chloride, 23 mmol/L of acetate and 23 mmol/L of gluconate. The hypotonic solution was made according to "existing recommendations in pediatric textbooks at the beginning of the study" and contained 80 mmol/L of sodium chloride and 20 mmol/L of potassium chloride in 5% dextrose.

The participants had all been admitted to Oulu University Hospital due to acute illness, usually respiratory infections, gastroenteritis, or other viral infection, and needed intravenous fluid therapy.

Hospitalization lasted a mean of 2.3 days, with intravenous fluids administered for 29 hours on average.

"We excluded patients with a severe electrolyte disorder already at the emergency department, patients with a kidney or liver failure, or a malignancy which required a specific fluid therapy protocol. There were only a few such patients," Dr. Tapiainen said. "We did not recruit any surgical-trauma patients. Otherwise, the results are applicable to most acutely ill pediatric patients needing fluid therapy."

Twenty percent of the children receiving isotonic fluid developed one or more clinically significant electrolyte disorders, the primary outcome, compared to just 2.9% of those on hypotonic fluid (P<0.001).

Hypokalemia accounted almost exclusively for this difference, which corresponded to a number needed to harm of six, the researchers report in JAMA Pediatrics.

Severe hypokalemia (<3.0 mmol/L) was more common in patients getting isotonic fluid (2.6% vs. 0.3%, P=0.02), as was hypernatremia (1.3% vs. 0%, P=0.04).

There was no significant difference in mild hyponatremia between patients getting isotonic fluid (2.3%) versus hypotonic fluid (3.6%, P=0.33). No patients developed severe hyponatremia (<132 mmol/L).

One patient receiving isotonic fluid was transferred to the pediatric intensive-care unit due to severe hypokalemia on the third day of fluid therapy.

"Electrolyte disorders were not prevented by the open study design, which allowed physicians to change fluid therapy during hospitalization," the researchers note.

They also found greater weight gain during the hospitalization among children receiving isotonic fluid (279 g vs. 195 g, P=0.02). Dr. Tapiainen said the difference "might imply a risk of water retention, due to a high concentration of sodium, in some children. This is an aspect which needs to be considered as a potential risk in vulnerable patient groups."

She concluded, "We hope that the findings help to further improve the clinical practice guidelines in the future. In particular, the risk of hypokalemia when using commercially available plasma-like isotonic fluid products needs to be considered."

But the AAP's Dr. Moritz said the study did not alter their recommendations, which do not apply to patients with "voluminous watery diarrhea" and have the stated purpose of preventing hyponatremia.

The guideline also specifically advises that isotonic fluids should have "appropriate potassium chloride," which means that "Patients who are hypokalemic should have KCL added to their IVFs," said Dr. Moritz.

"The patients with hypokalemia during the study likely had hypokalemia at presentation," he told Reuters Health. "It is not surprising that there was less hypokalemia in patients receiving potassium in their IVFs."

Dr. Moritz also noted that patients getting hypotonic fluids had a significantly higher incidence of acidosis (26% vs. 5.3%), which was not counted as a clinically significant electrolyte abnormality.

"There is no justification for giving hypotonic fluids," he concluded. "IVFs that are not balanced solutions are acidogenic in comparison to balanced solutions. There are commercially available isotonic fluids with potassium added such as D5 0.9NS and D5 Ringer Lactate with 20 mEq KCl."

Baxter did not respond to a request for comments.

The study had no commercial funding.

SOURCE: https://bit.ly/3jzJGmp JAMA Pediatrics, online October 26, 2020.

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