Association between intravenous chloride load during resuscitation and in-hospital mortality among patients with SIRS

Abstract

Purpose: Recent data suggest that both elevated serum chloride levels and volume overload may be harmful during fluid resuscitation. The purpose of this study was to examine the relationship between the intravenous chloride load and in-hospital mortality among patients with systemic inflammatory response syndrome (SIRS), with and without adjustment for the crystalloid volume administered.

Methods: We conducted a retrospective analysis of 109,836 patients ≥ 18 years old that met criteria for SIRS and received fluid resuscitation with crystalloids. We examined the association between changes in serum chloride concentration, the administered chloride load and fluid volume, and the 'volume-adjusted chloride load' and in-hospital mortality.

Results: In general, increases in the serum chloride concentration were associated with increased mortality. Mortality was lowest (3.7%) among patients with minimal increases in serum chloride concentration (0-10 mmol/L) and when the total administered chloride load was low (3.5% among patients receiving 100-200 mmol; P < 0.05 versus patients receiving ≥ 500 mmol). After controlling for crystalloid fluid volume, mortality was lowest (2.6%) when the volume-adjusted chloride load was 105-115 mmol/L. With adjustment for severity of illness, the odds of mortality increased (1.094, 95% CI 1.062, 1.127) with increasing volume-adjusted chloride load (≥ 105 mmol/L).

Conclusions: Among patients with SIRS, a fluid resuscitation strategy employing lower chloride loads was associated with lower in-hospital mortality. This association was independent of the total fluid volume administered and remained significant after adjustment for severity of illness, supporting the hypothesis that crystalloids with lower chloride content may be preferable for managing patients with SIRS.

Figures

Fig. 1

Relationship between the change in serum chloride concentration (Δ serum [Cl−]) and in-hospital mortality in patients meeting SIRS criteria and receiving >500 mL IV crystalloid fluids within 2 days of SIRS qualification. Overall, 99.8 % of patients (n = 109,658) experienced a change in serum chloride of 0–30 mmol/L. Data are fitted with a linear function (solidline), weighted on the basis of the number of patients in each Δ serum [Cl−] group. Dashed lines represent 95 % confidence interval

Fig. 2

Relationship between chloride load received within 72 h following SIRS qualification and in-hospital mortality (a). Relationship between IV fluid volume received within 72 h of SIRS qualification and in-hospital mortality (b). Regression lines (solidlines) in both panels represent a cubic polynomial fit and are weighted on basis of the number of patients receiving given amounts of total chloride or IV fluid. Dashed lines represent 95 % confidence interval

Fig. 3

Relationship between chloride load received via IV resuscitation fluids within 72 h following SIRS qualification and in-hospital mortality, stratified by total resuscitation fluid volume received. In the R 2 = 0.99). For the 1,500–3,000 through 6,000–7,500 mL groups, there was an increasingly positive association (increased mortality with increasing chloride load) for each incremental volume increase (1,500–3,000 mL: slope = 0.003, R2 = 0.11; 3,000–4,500 mL: slope = 0.01, R2 = 0.60; 4,500–6,000 mL: slope = 0.02, R2 = 0.76; 6,000–7,500 mL: slope = 0.03, R2 = 0.89; >7,500 mL: slope = 0.01, R2 = 0.32)

Fig. 4

Relationship between volume-adjusted chloride load received within 72 h following SIRS qualification and in-hospital mortality. Regression line (solidline) represents a cubic polynomial fit and is weighted on the basis of the number of patients receiving each given amount of volume-adjusted chloride. Dashed lines represent 95 % confidence interval. Insettable presents unadjusted and APS-adjusted mortality odds ratio (OR) associated with 10 mmol/L incremental increases in volume-adjusted chloride load for patients with volume-adjusted chloride load <105 and ≥105 mmol/L, respectively. Separate ORs were analysed for patients receiving <105 and ≥105 mmol/L given that (1) >97 % of patients received a volume-adjust chloride load ≥105 mmol/L, (2) lowest mortality was observed in patients receiving 105–115 mmol/L chloride and (3) 105 mmol/L approximates the established upper limit of normal serum chloride concentration [30]