Risk of Electrolyte Disorders in Acutely Ill Children Receiving Commercially Available Plasmalike Isotonic Fluids: A Randomized Clinical Trial

Abstract

Importance: The use of isotonic fluid therapy is currently recommended in children, but there is limited evidence of optimal fluid therapy in acutely ill children.

Objective: To evaluate the risk for electrolyte disorders, including hyponatremia, hypernatremia, and hypokalemia, and the risk of fluid retention in acutely ill children receiving commercially available plasmalike isotonic fluid therapy.

Design, setting, and participants: This unblinded, randomized clinical pragmatic trial was conducted at the pediatric emergency department of Oulu University Hospital, Finland, from October 3, 2016, through April 15, 2019. Eligible study subjects (N = 614) were between 6 months and 12 years of age, required hospitalization due to an acute illness, and needed intravenous fluid therapy. Exclusion criteria included a plasma sodium concentration of less than 130 mmol/L or greater than 150 mmol/L on admission; a plasma potassium concentration of less than 3.0 mmol/L on admission; clinical need of fluid therapy with 10% glucose solution; a history of diabetes, diabetic ketoacidosis, or diabetes insipidus; a need for renal replacement therapy; severe liver disease; pediatric cancer requiring protocol-determined chemotherapy hydration; and inborn errors of metabolism. All outcomes and samples size were prespecified except those clearly marked as exploratory post hoc analyses. All analyses were intention to treat.

Interventions: Acutely ill children were randomized to receive commercially available plasmalike isotonic fluid therapy (140 mmol/L of sodium and 5 mmol/L potassium in 5% dextrose) or moderately hypotonic fluid therapy (80 mmol/L sodium and 20 mmol/L potassium in 5% dextrose).

Main outcomes and measures: The primary outcome was the proportion of children with any clinically significant electrolyte disorder, defined as hypokalemia less than 3.5 mmol/L, hypernatremia greater than 148 mmol/L, or hyponatremia less than 132 mmol/L during hospitalization due to acute illness. The main secondary outcomes were the proportion of children with severe hypokalemia and weight change.

Results: There were 614 total study subjects (mean [SD] age, 4.0 [3.1] years; 315 children were boys [51%] and all 614 were Finnish speaking [100%]). Clinically significant electrolyte disorder was more common in children receiving plasmalike isotonic fluid therapy (61 of 308 patients [20%]) compared with those receiving moderately hypotonic fluid therapy (9 of 306 patients [2.9%]; 95% CI of the difference, 12%-22%; P < .001). The risk of developing electrolyte disorder was 6.7-fold greater in children receiving isotonic fluid therapy. Hypokalemia developed in 57 patients (19%) and hypernatremia developed in 4 patients (1.3%) receiving plasmalike isotonic fluid therapy. Weight change was greater in children receiving isotonic, plasmalike fluid therapy compared with those receiving mildly hypotonic fluids (mean weight gain, 279 vs 195 g; 95% CI, 16-154 g; P = .02).

Conclusions and relevance: In this randomized clinical trial, commercially available plasmalike isotonic fluid therapy markedly increased the risk for clinically significant electrolyte disorders, mostly due to hypokalemia, in acutely ill children compared with previously widely used moderately hypotonic fluid therapy containing 20 mmol/L of potassium.

Trial registration: ClinicalTrials.gov identifier: NCT02926989.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Lehtiranta reported receiving grants from the Finnish Pediatric Research Foundation, the Stiftelsen Alma and K.A. Snellman Foundation, and the Uskela Student Grant Foundation during the conduct of the study. Dr Kallio reported receiving grants from the Finnish Foundation for Pediatric Research during the conduct of the study. Dr Tapiainen reported receiving a grant from the Academy of Finland for part-time clinical research and from the Pediatric Research Foundation of Finland, used for the part-time salary of a study nurse in the pediatric clinical research projects. All products used in the study were paid for by the hospital as a part of routine patient care. No other disclosures were reported.

Figures

Figure 1.. Study Design

Altogether, 21 children were excluded owing to diabetes (5), pediatric cancer (1), severe hyponatremia at admission (1), severe hypokalemia at admission (1), age criterion not satisfied (7), parents did not understand the informed consent (1), and reason not specified by ED physician (5). The total number of children who both received fluid therapy and had at least 1 blood sample obtained was 283 in the isotonic group and 275 in the moderately hypotonic group. No children were lost to follow-up because the study ended at discharge from hospital. ED indicates emergency department.

Figure 2.. Potassium Concentrations at Different Time Points

Potassium levels are presented in the intention-to-treat population of children (N = 614) randomly allocated to receive plasmalike isotonic fluid therapy or moderately hypotonic fluid therapy with 80 mmol/L of sodium and 20 mmol/L of potassium. Each dot indicates the value of 1 study subject. The short horizontal lines indicate the mean value of the group in each time frame. The long horizontal line indicates the limit of clinically significant electrolyte disorder used in the statistical analysis. Potassium values indicating hyperkalemia >5.5. mmol/L were not verified in subsequent samples but were kept in the data unless the problem with the hemolysis was specifically marked in the laboratory sheets, resulting in hyperkalemia in 1 of 308 vs 2 of 306 (95% CI of the difference, –2% to 1.2%).

Figure 3.. Sodium Concentrations at Different Time Points

Sodium levels are presented in the intention-to-treat population of children (N = 614) randomly allocated to receive plasmalike isotonic fluid therapy or moderately hypotonic fluid therapy with 80 mmol/L of sodium and 20 mmol/L of potassium. Each dot indicates the value of 1 study subject. The short horizontal lines indicate the mean value of the group in each time frame. The long horizontal line indicates the limit of clinically significant electrolyte disorder used in the statistical analysis.