154 compared to 54 mmol per liter of sodium in intravenous maintenance fluid therapy for adult patients undergoing major thoracic surgery (TOPMAST): a single-center randomized controlled double-blind trial

Abstract

Purpose: To determine the effects of the sodium content of maintenance fluid therapy on cumulative fluid balance and electrolyte disorders.

Methods: We performed a randomized controlled trial of adults undergoing major thoracic surgery, randomly assigned (1:1) to receive maintenance fluids containing 154 mmol/L (Na154) or 54 mmol/L (Na54) of sodium from the start of surgery until their discharge from the ICU, the occurrence of a serious adverse event or the third postoperative day at the latest. Investigators, caregivers and patients were blinded to the treatment. Primary outcome was cumulative fluid balance. Electrolyte disturbances were assessed as secondary endpoints, different adverse events and physiological markers as safety and exploratory endpoints.

Findings: We randomly assigned 70 patients; primary outcome data were available for 33 and 34 patients in the Na54 and Na154 treatment arms, respectively. Estimated cumulative fluid balance at 72 h was 1369 mL (95% CI 601-2137) more positive in the Na154 arm (p < 0.001), despite comparable non-study fluid sources. Hyponatremia < 135 mmol/L was encountered in four patients (11.8%) under Na54 compared to none under Na154 (p = 0.04), but there was no significantly more hyponatremia < 130 mmol/L (1 versus 0; p = 0.31). There was more hyperchloremia > 109 mmol/L under Na154 (24/35 patients, 68.6%) than under Na54 (4/34 patients, 11.8%) (p < 0.001). The treating clinicians discontinued the study due to clinical or radiographic fluid overload in six patients receiving Na154 compared to one patient under Na54 (excess risk 14.2%; 95% CI - 0.2-30.4%, p = 0.05).

Conclusions: In adult surgical patients, sodium-rich maintenance solutions were associated with a more positive cumulative fluid balance and hyperchloremia; hypotonic fluids were associated with mild and asymptomatic hyponatremia.

Keywords: Chloride; Fluid balance; Fluid overload; Hyperchloremia; Hyponatremia; Maintenance fluid therapy; Sodium.

Fig. 1

Cohort derivation plot

Fig. 2

Cumulative fluid balance over the course of each study period. Black lines are individual observations of cumulative fluid balance over time per subject. Colored lines are the marginal means estimated using the mixed effects model; the shaded areas represent 95% confidence intervals. Fluid balance was estimated at 72 h (dashed line), as this is a typical duration for maintenance fluid therapy in the perioperative setting and the maximum duration of study treatment in the current study. The positive fluid balance at baseline is fluids that were administered immediately before surgery

Fig. 3

Serum levels of electrolytes (sodium and chloride), markers of kidney function (creatinine) and kidney injury (NGAL), and markers of hypovolemia-induced activation of the renin–angiotensin–aldosterone system (aldosterone) and capillary leakage (albumin) over the course of the treatment periods. In-graph p values are for the difference between the two fluids using random intercept models with treatment and time (categorical) as fixed effects, the baseline value as covariate and all subsequent values as outcomes. Colored lines resemble the median value at baseline for each fluid. Black dashed lines represent the electrolytes’ normal range. # indicates significantly different from baseline at a fluid-specific level (p < 0.05, Holm-adjusted to correct for multiple testing). n can be higher than the number of randomized patients when two measurements happened in one patient within the same 12-h time frame