Pre-emptive use of glucose 5% as the standard drug solvent reduces hypernatremia in critically ill patients

Abstract

Background: Hypernatremia presents a common complication in intensive care unit (ICU) patients, associated with increased mortality and length of stay. This study investigates the effect of sodium chloride 0.9% compared with glucose 5% solution as the standard intravenous drug diluent on the prevalence of hypernatremia in a medical ICU.

Methods: This is a retrospective before-and-after study comparing two consecutive patient groups before and after the standard drug solvent was changed from sodium chloride 0.9% to glucose 5% solution for compatible medications. A total of 265 adult COVID-19 patients admitted between October 2020 and March 2021 to the study ICU were included, with 161 patients in the timeframe when sodium chloride 0.9% was employed as the standard drug solvent and 104 patients when glucose 5% was used. Routine sodium measurements from arterial and venous blood gases, along with heparinized lithium plasma, were analyzed. The daily sodium concentrations and the prevalence of severe hypernatremia (>150 mmol/l) were assessed during the first 8 days after ICU admission.

Results: Baseline characteristics were similar between the two groups. The cumulative volume of intravenous drug diluents was comparable. In the glucose 5% group, about half of the total drug diluent volume was glucose 5% [mean (SD): 2251.6 (2355.4) ml], compared to 135.0 (746.9) ml (P < .001) in the control group. Average sodium concentrations diverged after day two, with the glucose 5% group consistently showing lower sodium levels (mean difference of ∼2.5 mmol/l). Severe hypernatremia occurred less frequently in the glucose 5% group (6.6% vs. 20%).

Conclusion: Glucose 5% solution as the standard intravenous drug solvent significantly reduced sodium concentrations and the occurrence of severe hypernatremia. This simple modification in solvent choice may serve as a preventive strategy against hypernatremia in the ICU. Further prospective research is necessary to determine associated clinical outcomes.

Trial registration: The trial was registered in the German Clinical Trials Register (DRKS00031877).

Keywords: drug diluent; drug solvent; glucose 5%; hypernatremia; sodium chloride 0.9%.

Figure 1:

Patient disposition: 268 patients were admitted to the ICU between 1 October 2020 and 30 March 2021. After excluding three patients due to missing sodium measurements, 265 were included in the analysis. In 161 patients (admitted before 8 January 2021) sodium chloride 0.9% and 104 patients (admitted from 8 January 2021) glucose 5% were used as the drug solvents. Patients identified as crossovers were excluded from the sodium analysis beyond the specific cutoff dates of 7 January 2021 for the control group and 30 March 2021 for the intervention group. These crossovers occurred because the standard drug solvent used during their ICU stay was altered.

Figure 2:

Sodium concentration, hypernatremia prevalence, chloride, and bicarbonate concentrations in ICU patients. (a) The mean plasma sodium level (±95% CI) during the first 8 days after ICU admission for both the glucose 5% group and the control group. Day 0 represents the day of ICU admission. (b) The prevalence of hypernatremia (±95% CI) stratified by severity for the first 8 days following ICU admission. (c) The mean chloride level (±95% CI). (d) The mean bicarbonate level (±95% CI). In cases where sodium, chloride, or bicarbonate levels were measured multiple times per day for a patient, the daily mean was calculated for analysis.

Figure 3:

Volume of intravenous drug diluents, daily fluid balance, glucose concentration and insulin dose. Shown are (a) the cumulative volume of intravenous drug diluents (ml), (b) the cumulative total fluid balance (ml) (mean ± 95% CI), (c) the glucose levels (mg/dl) (mean ± 95% CI), and (d) the insulin dose (IU) (mean ± 95% CI) in the glucose 5% and control group. If glucose levels were measured multiple times per day the highest value was used to calculate the mean.

Figure 4:

Sodium concentrations in study and non-study ICUs during control and glucose 5% time periods. The figure displays the mean plasma sodium level (±95% CI) for the first 8 days following admission to the ICU in both study and non-study ICUs during the control and glucose 5% time periods. In non-study ICUs, sodium chloride 0.9% continued to be the standard drug solvent. Day 0 represents the day of ICU admission.